Gender Differences in Autoimmune Diseases

Size: px
Start display at page:

Download "Gender Differences in Autoimmune Diseases"

Transcription

1 //9 Impact of Gender on the Pathogenesis of Crohn s Disease Theresa T. Pizarro Department of Pathology, CWRU Gender Differences in Autoimmune Diseases n Autoimmune diseases affect ~.7-. million people n Disproportionate occurrence (~%) in female population n Magnitude of gender bias is disease specific n Hashimoto s thyroiditis (:, female: male ratio) Lupus (:, female: male ratio) Chronic active hepatitis Sjogren s syndrome (7:, female: male ratio) Primary biliary cirrhosis Rheumatoid arthritis (:, female: male ratio) Multiple sclerosis (:, female: male ratio) Diabetes mellitis type (:, female: male ratio) n Currently, pathogenic mechanism(s) underlying gender bias in autoimmunity is unknown

2 //9 Gender Differences in IBD (Crohn s disease) n Effects of hormonal surges during pregnancy and post-partum appear to impact symptom activity in CD (Crohn et al., NY State J. Med. 9) n Increased incidence of CD in Turner s Syndrome patients (Price, J. Med. Genet. 979) n Susceptibility locus on ChrX that may be associated with a genetic predisposition to CD (Vermeire et al., Gastroenterol. ) n Slight increase in incidence of CD in females compared to males (.:, female: male ratio) (Hanauer et al., Inflamm. Bowel Dis. ) n Female CD patients more likely to experience severe disease manifestations and lower health-related quality of life (Saibeni et al., Hepatogastroenterol. ) n High-frequency TLR haplotypes (located on ChrX locus) are associated with both UC and CD in females (Saruta et al., IBD Journal 9) Gender Differences in Animal Models of IBD n Treatment with a highly selective orally active estrogen receptor (Erb) ligand treated Th-mediated colitis (Verdu et al., Am. J. Physiol. ) n Presence of an X-linked susceptibility loci in the /YitFc mouse strain (Kozaiwa et al., Gastroenterol. ) n Deletion of the X-linked immunodeficiency gene, Wiskott- Aldrich Syndrome protein (WASP), results in Th-mediated colitis (Nguyen et al., Gastroenterol. 7)

3 //9 Features of the /YitFc () mouse model of experimental Crohn s disease n Spontaneous ileitis without chemical, genetic or immunologic manipulation n % penetrance by wks; persistence of phenotype up to wks of age n Closely resembles human CD for disease location and histologic features n Disease mediated by both Th and Th cytokines n Responsive to standard CD therapies (i.e. steroids, anti-tnf) Histologic features of mouse strain n Segmental, discontinuous inflammation n Villous blunting, infiltration of PMNs, mononuclear cells in LP and submucosa n Apthous inflammatory lesions n Transmural inflammation n Granulomas n Cryptitis, Crypt microabscesses n Basal plasmacytolysis Kosiewicz, et al., J. Clin. Invest.

4 //9 Early & severe ileal inflammation in - females week- Male week- Female Total Inflammatory Index Male Female 7 9 Age (weeks) Villous Distortion Score 7 9 Active Inflammatory Score 7 9 Chronic Inflammatory Score 7 9 Age (weeks) Age (weeks) Age (weeks) Suggestive QTL by analysis of extreme phenotypes Chr Chr Chr 9 Chr X DXMit7 D9Mit DMit9 DMit Sugawara, et al., Gastroenterol. PPARg E-cadherin a/b-defensins Kozaiwa, et al., Gastroenterol. b-catenin JAM-C cingulin-like IL- MyD IL-R claudin- FoxP

5 //9 Human Chr X Mouse Chr X Xp.. Foxp A. Foxp (.cm) Xq.-q Cldn IRAK (9. cm) A 7. NEMO Xq IRAK NEMO F Cldn Epithelial permeability is increased in mice and occurs prior to the onset of inflammation A Small Intestine (Lactulose/Mannitol FE) AKR B Ileal Inflammatory Score AKR C Ileum MPO Activity (U/mg tissue) AKR Colon (Sucralose FE) Age (weeks) Colon Inflammatory Score 9 Age (weeks) Colon MPO Activ ity (U/mg tissue) 9 Age (weeks) Olson, et al., J. Exp. Med.,

6 //9 Altered epithelial TJ protein in young, uninflamed compared to control AKR ILEUM COLON claudin- mrna Expression mrna Expression mrna Expression.... AKR claudin- claudin- claudin- claudin- #... claudin- claudin- claudin- claudin- # Olson, et al., J. Exp. Med., occludin occludin Total Ileal Inflammation. Inflammatory Score..... Lactulose:Mannitol FE Ratio native Small Intestinal Permeability Chr 7 (cont.) Chr PPARg Chr Chr 9 Chr X E-cadherin b-catenin claudin- a/b-defensins JAM-C FoxP cingulin-like IL- MyD IL-R

7 //9 What is the mechanism(s) for the differential response to estrogens in male vs female mice? Impact of ER isotypes in males vs females Role of Tregs in the manifestation of ileitis No significant difference in serum estrogen levels comparing vs AKR (control) females Circulating E is not responsible for modulating ileitis Disease may be due to differential expression of ER isotypes 7

8 //9 Differential expression of ER isotypes on MLN cells from and control mice ER-α Actin AKR F M F M ERa/Actin Ratio P<. vs. other experimental groups ER-β Actin ERḇ / Actin Ratio F M M F AKR P<. vs. other experimental groups Characterization of MLN Treg (FoxP) subsets Mouse X- chromosome A. FoxP (.cm) A A. A. A A A A 7. A 7. B C C D E E F F F F Rivera-Nieves, et al., Gastroenterol. FACS characterization of male vs. female Tregs

9 //9 Overview: distinct populations of Treg cells Naïve T Natural Tregs Other T cells populations TGF-β, IL- FoxP Th Figure from Walker Lucy SK, Immunol cell biol, 7; : - 7 Recently described Folate receptor marker; FR was included for characterizing distinct populations of Treg; in addition to traditional marker, FoxP Sakaguchi et al,immunity; 7 High population of MLN ntregs exist in males vs females FoxP hi A. Male Female AKR Male. ±.7. ±.. ±. AKR Female. ±.7 CDCD FRhi.7 ±.. ±.. ±.7. ±.7 CDCD Natural Tregs CDFoxphi higher in males Putative effector T cells, CDFoxPlo and CDFRlo cells higher in -F 9

10 //9 ERβ agonist influences MLN Treg marker expression FoxP/Actin 9 FoxP IL- (Pg/ml) PPT IL- P<. vs. other experimental groups DPN CTRL M F M F AKR M F M F AKR M F M F AKR P<. vs. other experimental groups TGF-b (Pg/ml) 7 M F M F TGF-β M F M F M F M F PPT DPN CTRL M F M F M F M F M F M F AKR AKR AKR -F Tregs are functionally more active than -F males females AKR males AKR females M M M Treg suppression activity = fold difference of percent divided T- effector cells (alone) : Teffector + Treg In co-culture experiment, ratio of T-effector: Treg used was : M= 7 h M= 9 h M= h

11 //9 Summary of Potential Pathogenic Mechanisms Underlying Gender Bias in Crohn s Disease Immunological factors Environmental Factors Genetic Factors Loss of Selftolerance Direct immune system towards Th/Th responses Dysfunctional regulatory mechanisms Crohn s Disease Sex hormones (androgens, estrogens) ChrX plays role? fetal-maternal microchimerism confer susceptibility?

Innate immune regulation of T-helper (Th) cell homeostasis in the intestine

Innate immune regulation of T-helper (Th) cell homeostasis in the intestine Innate immune regulation of T-helper (Th) cell homeostasis in the intestine Masayuki Fukata, MD, Ph.D. Research Scientist II Division of Gastroenterology, Department of Medicine, F. Widjaja Foundation,

More information

Autoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens

Autoimmunity. Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmunity Autoimmunity arises because of defects in central or peripheral tolerance of lymphocytes to selfantigens Autoimmune disease can be caused to primary defects in B cells, T cells and possibly

More information

12/10/2009. Department of Pathology, Case Western Reserve University. Mucosal Cytokine Network in IBD

12/10/2009. Department of Pathology, Case Western Reserve University. Mucosal Cytokine Network in IBD Cytokine-Mediated Inflammation in IBD Theresa T. Pizarro Department of Pathology, Case Western Reserve University Mucosal Cytokine Network in IBD Andoh, et al., 2008 1 Interleukin-1 (IL-1) Family Cytokine

More information

Histological and immunological characteristics of colitis associated with anti-ctla 4 antibody therapy

Histological and immunological characteristics of colitis associated with anti-ctla 4 antibody therapy Histological and immunological characteristics of colitis associated with anti-ctla 4 antibody therapy M. Perdiki 2, G. Bamias 1, D. Pouloudi 2, H. Gogas 3, I. Delladetsima 2 1 Academic Dpt. of Gastroenterology,

More information

Murine Models of. Inflammatory Bowel Disease. Outline. Laura P. Hale, M.D. Ph.D. Professor of Pathology Duke University Medical Center

Murine Models of. Inflammatory Bowel Disease. Outline. Laura P. Hale, M.D. Ph.D. Professor of Pathology Duke University Medical Center Murine Models of Inflammatory Bowel Disease Laura P. Hale, M.D. Ph.D. Professor of Pathology Duke University Medical Center September 19, 2017 Outline Review of IBD in humans Murine models of IBD Tissue

More information

Tolerance 2. Regulatory T cells; why tolerance fails. FOCiS. Lecture outline. Regulatory T cells. Regulatory T cells: functions and clinical relevance

Tolerance 2. Regulatory T cells; why tolerance fails. FOCiS. Lecture outline. Regulatory T cells. Regulatory T cells: functions and clinical relevance 1 Tolerance 2. Regulatory T cells; why tolerance fails Abul K. Abbas UCSF FOCiS 2 Lecture outline Regulatory T cells: functions and clinical relevance Pathogenesis of autoimmunity: why selftolerance fails

More information

Central tolerance. Mechanisms of Immune Tolerance. Regulation of the T cell response

Central tolerance. Mechanisms of Immune Tolerance. Regulation of the T cell response Immunoregulation: A balance between activation and suppression that achieves an efficient immune response without damaging the host. Mechanisms of Immune Tolerance ACTIVATION (immunity) SUPPRESSION (tolerance)

More information

Mechanisms of Immune Tolerance

Mechanisms of Immune Tolerance Immunoregulation: A balance between activation and suppression that achieves an efficient immune response without damaging the host. ACTIVATION (immunity) SUPPRESSION (tolerance) Autoimmunity Immunodeficiency

More information

Tolerance 2. Regulatory T cells; why tolerance fails. Abul K. Abbas UCSF. FOCiS

Tolerance 2. Regulatory T cells; why tolerance fails. Abul K. Abbas UCSF. FOCiS 1 Tolerance 2. Regulatory T cells; why tolerance fails Abul K. Abbas UCSF FOCiS 2 Lecture outline Regulatory T cells: functions and clinical relevance Pathogenesis of autoimmunity: why selftolerance fails

More information

Grup de fisiologia digestiva i adaptacions nutricionals Institut de Nutrició i Seguretat Alimentaria

Grup de fisiologia digestiva i adaptacions nutricionals Institut de Nutrició i Seguretat Alimentaria Grup de fisiologia digestiva i adaptacions nutricionals Institut de Nutrició i Seguretat Alimentaria 1 Outline Weaning and the consequences of stress Animal blood plasma Spray-drying SDP SDP in a model

More information

Tolerance, autoimmunity and the pathogenesis of immunemediated inflammatory diseases. Abul K. Abbas UCSF

Tolerance, autoimmunity and the pathogenesis of immunemediated inflammatory diseases. Abul K. Abbas UCSF Tolerance, autoimmunity and the pathogenesis of immunemediated inflammatory diseases Abul K. Abbas UCSF Balancing lymphocyte activation and control Activation Effector T cells Tolerance Regulatory T cells

More information

What is Autoimmunity?

What is Autoimmunity? Autoimmunity What is Autoimmunity? Robert Beatty MCB150 Autoimmunity is an immune response to self antigens that results in disease. The immune response to self is a result of a breakdown in immune tolerance.

More information

What is Autoimmunity?

What is Autoimmunity? Autoimmunity What is Autoimmunity? Robert Beatty MCB150 Autoimmunity is an immune response to self antigens that results in disease. The immune response to self is a result of a breakdown in immune tolerance.

More information

Genetics. Environment. You Are Only 10% Human. Pathogenesis of IBD. Advances in the Pathogenesis of IBD: Genetics Leads to Function IBD

Genetics. Environment. You Are Only 10% Human. Pathogenesis of IBD. Advances in the Pathogenesis of IBD: Genetics Leads to Function IBD Advances in the Pathogenesis of IBD: Genetics Leads to Function Pathogenesis of IBD Environmental Factors Microbes Scott Plevy, MD Associate Professor of Medicine, Microbiology & Immunology UNC School

More information

Control of intestinal inflammation by regulatory T cells

Control of intestinal inflammation by regulatory T cells Control of intestinal inflammation by regulatory T cells Fiona Powrie Sir William Dunn School of Pathology University of Oxford fiona.powrie@path.ox.ac.uk Regulatory T cells prevent immune pathology in

More information

Immunology, Faculty of Medicine University of Bari, Bari (Italy) Proprietà benefiche di latte, vino e olio extra vergine di oliva

Immunology, Faculty of Medicine University of Bari, Bari (Italy) Proprietà benefiche di latte, vino e olio extra vergine di oliva Immunology, Faculty of Medicine University of Bari, Bari (Italy) Proprietà benefiche di latte, vino e olio extra vergine di oliva Professor Emilio Jirillo basketball court (about 400 m 2 ) mucosa-associated

More information

IL-12 family members in experimental colitis. Markus F. Neurath I. Medical Clinic Johannes Gutenberg-University Mainz, Germany

IL-12 family members in experimental colitis. Markus F. Neurath I. Medical Clinic Johannes Gutenberg-University Mainz, Germany IL-12 family members in experimental colitis Markus F. Neurath I. Medical Clinic Johannes Gutenberg-University Mainz, Germany IBD - Pathogenesis Genetic Predisposition Bacterial Antigens Activation of

More information

Unique Aspects of the Neonatal Immune System Provide Clues to the Pathogenesis of Biliary Atresia. Disclosures. Objectives

Unique Aspects of the Neonatal Immune System Provide Clues to the Pathogenesis of Biliary Atresia. Disclosures. Objectives Unique Aspects of the Neonatal Immune System Provide Clues to the Pathogenesis of Biliary Atresia Cara L. Mack, MD Associate Professor of Pediatrics Pediatric GI, Hepatology & Nutrition Children s Hospital

More information

Supplemental Materials

Supplemental Materials Supplemental Materials Programmed death one homolog maintains the pool size of regulatory T cells by promoting their differentiation and stability Qi Wang 1, Jianwei He 1, Dallas B. Flies 2, Liqun Luo

More information

The child under age 5 with inflammatory bowel disease

The child under age 5 with inflammatory bowel disease The child under age 5 with inflammatory bowel disease Athos Bousvaros MD, MPH Overview IBD as a manifestation of immune deficiency Chronic granulomatous disease Glycogen storage disease 1b Hermansky-Pudlak

More information

Intestinal Microbiota in Health and Disease

Intestinal Microbiota in Health and Disease Intestinal Microbiota in Health and Disease February 27, 2015 Master s Course in Gastroenterology Prof. Kathy McCoy 1 Overview Overview of Gut Microbiota Microbiota in Health Microbiota in Disease 2 Gut

More information

What is your diagnosis? a. Lymphocytic colitis. b. Collagenous colitis. c. Common variable immunodeficiency (CVID) associated colitis

What is your diagnosis? a. Lymphocytic colitis. b. Collagenous colitis. c. Common variable immunodeficiency (CVID) associated colitis Case History A 24 year old male presented with fatigue, fever, watery diarrhea, and a cough with sputum production for the past three weeks. His past medical history was significant for recurrent bouts

More information

ALLERGY AND AUTOIMMUNITY

ALLERGY AND AUTOIMMUNITY ALLERGY AND AUTOIMMUNITY Allergies and Autoimmunity Allergies and autoimmunity can be prevented It all starts in the gut It is more than preventing leaky gut IgE allergies do not necessarily involve leaky

More information

DNA vaccine, peripheral T-cell tolerance modulation 185

DNA vaccine, peripheral T-cell tolerance modulation 185 Subject Index Airway hyperresponsiveness (AHR) animal models 41 43 asthma inhibition 45 overview 41 mast cell modulation of T-cells 62 64 respiratory tolerance 40, 41 Tregs inhibition role 44 respiratory

More information

Cathepsin S Inhibitors for the Treatment of Inflammatory Bowel Disease. Therapeutic Area Partnerships Presentation.

Cathepsin S Inhibitors for the Treatment of Inflammatory Bowel Disease. Therapeutic Area Partnerships Presentation. Inhibitors for the Treatment of Inflammatory Bowel Disease Therapeutic Area Partnerships Presentation November 29, 2012 Cathepsin Cysteine Proteinases Fibrosis Cathepsin O Cathepsin B Cathepsin C Cathepsin

More information

Th17 Pathway Research By Bio-Plex

Th17 Pathway Research By Bio-Plex Th17 Pathway Research By Bio-Plex Zhiyang Shen, Senior Product Manager Bio-Rad Laboratories, Inc 2011 年 6 月 28 日星期二 T helper cell research Timeline: advances on T helper research. Figure depicts some of

More information

Supplemental Digital Content 1. Endoscopic and histolological findings in INR and FR study subjects

Supplemental Digital Content 1. Endoscopic and histolological findings in INR and FR study subjects Supplemental Digital Content 1. Endoscopic and histolological findings in INR and FR study subjects Patient Group Macroscopic examination Ileum Histology Colon/rectum Histology 1 INR Normal Acute and chronic

More information

Supplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence

Supplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence Supplemental Table 1. Primers used for RT-PCR analysis of inflammatory cytokines Gene Primer Sequence IL-1α Forward primer 5 -CAAGATGGCCAAAGTTCGTGAC-3' Reverse primer 5 -GTCTCATGAAGTGAGCCATAGC-3 IL-1β

More information

Effector T Cells and

Effector T Cells and 1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New

More information

Understanding clinical aspects of Crohn s disease and ulcerative colitis: Implications for the basic scientist

Understanding clinical aspects of Crohn s disease and ulcerative colitis: Implications for the basic scientist Understanding clinical aspects of Crohn s disease and ulcerative colitis: Implications for the basic scientist Scott Plevy, MD Associate Professor of Medicine, Microbiology & Immunology UNC School of Medicine

More information

Multiple Sclerosis and Neuroinflammation: Considering Gender differences to design therapeutic agents HALINA OFFNER

Multiple Sclerosis and Neuroinflammation: Considering Gender differences to design therapeutic agents HALINA OFFNER Multiple Sclerosis and Neuroinflammation: Considering Gender differences to design therapeutic agents HALINA OFFNER Sex differences in autoimmune disease Ratio Target Sex distribution of major autoimmune

More information

Patho Basic Chronic Inflammatory Bowel Diseases. Jürg Vosbeck Pathology

Patho Basic Chronic Inflammatory Bowel Diseases. Jürg Vosbeck Pathology Patho Basic Chronic Inflammatory Bowel Diseases Jürg Vosbeck Pathology General Group of chronic relapsing diseases with chronic bloody or watery diarrhea Usually ulcerative colitis (UC) or Crohn s disease

More information

Immunological Tolerance

Immunological Tolerance Immunological Tolerance Introduction Definition: Unresponsiveness to an antigen that is induced by exposure to that antigen Tolerogen = tolerogenic antigen = antigen that induces tolerance Important for

More information

Autoimmunity and Primary Immune Deficiency

Autoimmunity and Primary Immune Deficiency Autoimmunity and Primary Immune Deficiency Mark Ballow, MD Division of Allergy & Immunology USF Morsani School of Medicine Johns Hopkins All Children s Hospital St Petersburg, FL The Immune System What

More information

Regulatory B cells in autoimmunity. Liwei Lu University of Hong Kong, China

Regulatory B cells in autoimmunity. Liwei Lu University of Hong Kong, China Regulatory B cells in autoimmunity Liwei Lu University of Hong Kong, China Multiple functions of B cells in immunity LeBien and Tedder, Blood (2008) B cell functions in autoimmune pathogenesis The Immunopathogensis

More information

Kids Like to Break the Rules: Gastrointestinal Pathology in Children

Kids Like to Break the Rules: Gastrointestinal Pathology in Children Kids Like to Break the Rules: Gastrointestinal Pathology in Children Jeffrey Goldsmith MD Director of Surgical Pathology, Beth Israel Deaconess Medical Center; Consultant in Gastrointestinal Pathology,

More information

Bachelor of Chinese Medicine ( ) AUTOIMMUNE DISEASES

Bachelor of Chinese Medicine ( ) AUTOIMMUNE DISEASES Bachelor of Chinese Medicine (2002 2003) BCM II Dr. EYT Chan February 6, 2003 9:30 am 1:00 pm Rm 134 UPB AUTOIMMUNE DISEASES 1. Introduction Diseases may be the consequence of an aberrant immune response,

More information

Therapeutic options to modulate intestinal barrier

Therapeutic options to modulate intestinal barrier 15 + 5 min J.D. Schulzke Dept. of General Medicine Therapeutic options to modulate intestinal barrier What makes up epithelial barrier function? ions/h 2 O antigens/bacteria tight junction apoptoses erosions

More information

Supplementary Material

Supplementary Material Supplementary Material Fig. S1. Gpa33 -/- mice do not express Gpa33 mrna or GPA33 protein. (A) The Gpa33 null allele contains a premature translational stop codon (STOP) in exon 2, and almost all of the

More information

D2 inhibits TLR2- initiated 12p40 transcription (-) TLR2 PGN MDP. MyD88 IRAK ECSIT TRAF6 NIK. Smallest unit of PGN muramyl dipeptide IKK.

D2 inhibits TLR2- initiated 12p40 transcription (-) TLR2 PGN MDP. MyD88 IRAK ECSIT TRAF6 NIK. Smallest unit of PGN muramyl dipeptide IKK. D2 inhibits TLR2- initiated 12p40 transcription CARD CARD NOD2 LRR RICK/Rip2 NIK MDP TRAF6 PGN TLR2 MyD88 IRAK ECSIT (-) IKK Smallest unit of PGN muramyl dipeptide IκB NF-κB atanabe et al, 2004 NF-κB IL-12p40

More information

Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn s disease

Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn s disease Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn s disease See related Commentary, pages 667-669. Michele M. Kosiewicz, 1 Cynthia C. Nast, 2 Anasuya Krishnan, 1 Jesus Rivera-Nieves,

More information

SUBDIVISIONS OF THE MUCOSA Distinct features of type I and type II mucosal surfaces

SUBDIVISIONS OF THE MUCOSA Distinct features of type I and type II mucosal surfaces Alessandra Pernis P&S 9-435 X53763 abp1@columbia.edu CHALLENGES FACED BY THE MUCOSAL SYSTEM SPECIALIZATION OF CELLS INVOLVED IN MUCOSAL IMMUNITY ORGANIZATION OF THE MUCOSAL IMMUNE SYSTEM CLINICAL IMPLICATIONS

More information

Basic Immunology. Immunological tolerance. Cellular and molecular mechanisms of the immunological tolerance. Lecture 23 rd

Basic Immunology. Immunological tolerance. Cellular and molecular mechanisms of the immunological tolerance. Lecture 23 rd Basic Immunology Lecture 23 rd Immunological tolerance Cellular and molecular mechanisms of the immunological tolerance Tolerated skin grafts on MHC (H2) identical mice TOLERANCE & AUTOIMMUNITY Upon encountering

More information

Potential Rebalancing of the Immune System by Anti-CD52 Therapy

Potential Rebalancing of the Immune System by Anti-CD52 Therapy Potential Rebalancing of the Immune System by Anti-CD52 Therapy Johanne Kaplan, PhD VP Neuroimmunology Research Genzyme March 26, 2013 RESTRICTED USE SEE TRAINING MEMO 2011 DO Genzyme NOT 1COPY Corporation

More information

Reviewers' comments: Reviewer #1 (Remarks to the Author):

Reviewers' comments: Reviewer #1 (Remarks to the Author): Reviewers' comments: Reviewer #1 (Remarks to the Author): The manuscript by Sun et al., provide data showing that short-chain fatty acids produced by intestinal microbiota act through GPR43 to induced

More information

IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, psoriasis

IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, psoriasis IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, inhibits disease development in mouse models of psoriasis Weiwen e Ja Jiang, Fu-Gang Zhu, Dong Yu, Ekambar R. Kandimalla, a a, Nicola La Monica, and Sudhir

More information

IBD 101. Ronen Stein, MD Assistant Professor of Clinical Pediatrics Division of Gastroenterology, Hepatology, and Nutrition

IBD 101. Ronen Stein, MD Assistant Professor of Clinical Pediatrics Division of Gastroenterology, Hepatology, and Nutrition IBD 101 Ronen Stein, MD Assistant Professor of Clinical Pediatrics Division of Gastroenterology, Hepatology, and Nutrition Objectives Identify factors involved in the development of inflammatory bowel

More information

A Case of Inflammatory Bowel Disease

A Case of Inflammatory Bowel Disease A Case of Inflammatory Bowel Disease Dr Barrie Rathbone www.le.ac.uk 26 year old Polish woman Admitted as emergency under surgeons RUQ and RIF pain Abdominal pain had occurred intermittently for a few

More information

This is a free sample of content from Immune Tolerance. Click here for more information or to buy the book.

This is a free sample of content from Immune Tolerance. Click here for more information or to buy the book. A ACPAs. See Antibodies to citrullinated peptide antigens Activation-induced cell death (AICD), 25 AICD. See Activation-induced cell death AIRE, 3, 18 19, 24, 88, 103 104 AKT, 35 Alefacept, 136 ALPS. See

More information

Supplementary Figure 1 IL-27 IL

Supplementary Figure 1 IL-27 IL Tim-3 Supplementary Figure 1 Tc0 49.5 0.6 Tc1 63.5 0.84 Un 49.8 0.16 35.5 0.16 10 4 61.2 5.53 10 3 64.5 5.66 10 2 10 1 10 0 31 2.22 10 0 10 1 10 2 10 3 10 4 IL-10 28.2 1.69 IL-27 Supplementary Figure 1.

More information

HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER

HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER HLA TYPING AND EXPRESSION: POTENTIAL MARKER FOR IDENTIFYING EARLY DYSPLASIA AND STRATIFYING THE RISK FOR IBD-CANCER Megan Garrity, S. Breanndan Moore, M.D., William Sandborn, M.D., Vernon Pankratz, Ph.D.,

More information

Gut Microbiota and IBD. Vahedi. H M.D Associate Professor of Medicine DDRI

Gut Microbiota and IBD. Vahedi. H M.D Associate Professor of Medicine DDRI Gut Microbiota and IBD Vahedi. H M.D Associate Professor of Medicine DDRI 1393.3.1 2 GUT MICROBIOTA 100 Trillion Microbes - 10 times more than cells in our body Collective weight of about 1kg in human

More information

Lecture outline. Immunological tolerance and immune regulation. Central and peripheral tolerance. Inhibitory receptors of T cells. Regulatory T cells

Lecture outline. Immunological tolerance and immune regulation. Central and peripheral tolerance. Inhibitory receptors of T cells. Regulatory T cells 1 Immunological tolerance and immune regulation Abul K. Abbas UCSF 2 Lecture outline Central and peripheral tolerance Inhibitory receptors of T cells Regulatory T cells 1 The immunological equilibrium:

More information

Immune Tolerance. Kyeong Cheon Jung. Department of Pathology Seoul National University College of Medicine

Immune Tolerance. Kyeong Cheon Jung. Department of Pathology Seoul National University College of Medicine Immune Tolerance Kyeong Cheon Jung Department of Pathology Seoul National University College of Medicine Immune tolerance Unresponsiveness to an antigen that is induced by previous exposure to that antigen

More information

IBD. Crohn s. Outline. Ulcerative colitis versus Crohn s disease: is biopsy useful? UC vs. Crohn s? Is it easy? Biopsy settings 21/07/2017 IBD

IBD. Crohn s. Outline. Ulcerative colitis versus Crohn s disease: is biopsy useful? UC vs. Crohn s? Is it easy? Biopsy settings 21/07/2017 IBD Outline Ulcerative colitis versus Crohn s disease: is biopsy useful? Roger Feakins Colorectal biopsies Ileal and upper GI biopsies Special situations New techniques Summary Inflammatory bowel disease (IBD)

More information

Relevant Disclosures

Relevant Disclosures 6/18/215 Therapeutic developments for autoimmune demyelinating diseases: Musings from a MD (Mouse Doctor) Michael K. Racke, M.D. May 28, 215 Relevant Disclosures Editorial Boards for Journal of Neuroimmunology,

More information

Topic (Final-03): Immunologic Tolerance and Autoimmunity-Part II

Topic (Final-03): Immunologic Tolerance and Autoimmunity-Part II Topic (Final-03): Immunologic Tolerance and Autoimmunity-Part II MECHANISMS OF AUTOIMMUNITY The possibility that an individual s immune system may react against autologous antigens and cause tissue injury

More information

Immunology 2011 Lecture 20 Autoimmunity 18 October

Immunology 2011 Lecture 20 Autoimmunity 18 October Immunology 2011 Lecture 20 Autoimmunity 18 October APC Antigen processing (dendritic cells, MΦ et al.) Antigen "presentation" Ag/Ab complexes Antigenspecific triggering B T ANTIGEN Proliferation Differentiation

More information

Type 1 Diabetes: Islet expressing GAD65 (green) with DAPI (Blue) Islet expressing Insulin (red) in 3D confocal imaging

Type 1 Diabetes: Islet expressing GAD65 (green) with DAPI (Blue) Islet expressing Insulin (red) in 3D confocal imaging Type 1 Diabetes: Our group has been studying autoimmune diabetes for many years. Recently, we have developed a humanized mouse model of Type 1 Diabetes (T1D). We believe this model will help understand

More information

Autoimmunity. By: Nadia Chanzu, PhD Student, UNITID Infectious Minds Presentation November 17, 2011

Autoimmunity. By: Nadia Chanzu, PhD Student, UNITID Infectious Minds Presentation November 17, 2011 Molecular Mechanisms of Autoimmunity By: Nadia Chanzu, PhD Student, UNITID Infectious Minds Presentation November 17, 2011 Introduction 3m Pick an organ, any organ... Autoimmunity can affect ANY organ/organ

More information

Genetics of Pediatric Inflammatory Bowel Disease

Genetics of Pediatric Inflammatory Bowel Disease Genetics of Pediatric Inflammatory Bowel Disease Judith Kelsen MD Assistant Professor of Pediatrics Division of Gastroenterology, Hepatology, and Nutrition IBD Education Day 2/9/2014 Objectives Brief overview

More information

AUTOIMMUNITY AND THE GUT

AUTOIMMUNITY AND THE GUT AUTOIMMUNITY AND THE GUT Autoimmunity The Past The rationale - All about a malfunctioning immune system The immune system is overactive to the point of attacking the body Avoid anything that stimulates

More information

Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.

Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Allergy and Immunology Review Corner: Chapter 19 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 19: Tolerance, Autoimmunity, and Autoinflammation Prepared

More information

Diseases of Immunity 2017 CL Davis General Pathology. Paul W. Snyder, DVM, PhD Experimental Pathology Laboratories, Inc.

Diseases of Immunity 2017 CL Davis General Pathology. Paul W. Snyder, DVM, PhD Experimental Pathology Laboratories, Inc. Diseases of Immunity 2017 CL Davis General Pathology Paul W. Snyder, DVM, PhD Experimental Pathology Laboratories, Inc. Autoimmunity Reflects a loss of immunologic tolerance Mechanisms Auto-antibodies

More information

Cardiac myosin-th17 responses promote heart failure in human myocarditis

Cardiac myosin-th17 responses promote heart failure in human myocarditis Cardiac myosin-th17 responses promote heart failure in human myocarditis Jennifer M. Myers,, Carol J. Cox, Madeleine W. Cunningham JCI Insight. 2016;1(9):e85851. https://doi.org/10.1172/jci.insight.85851.

More information

Oncologist-induced Disease of the GI tract: New Developments

Oncologist-induced Disease of the GI tract: New Developments Oncologist-induced Disease of the GI tract: New Developments Jeffrey D Goldsmith, MD Children s Hospital Boston, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, MA Everyone s on drugs

More information

Mechanisms of allergen-specific immunotherapy

Mechanisms of allergen-specific immunotherapy 2012 KAAACI/EAAS Spring Mechanisms of allergen-specific immunotherapy Woo-Jung Song, MD Division of Allergy and Clinical Immunology Department of Internal Medicine Seoul National University Hospital, Seoul,

More information

Cell-mediated Immunity

Cell-mediated Immunity Cellular & Molecular Immunology Cell-mediated Immunity Nicholas M. Ponzio, Ph.D. Department of Pathology & Laboratory Medicine April 6, 2009 Today s Presentation: Overview Cellular Interactions In Humoral

More information

Innate immunity as a therapeutic target in IBD. Elke Cario Division of Gastroenterology & Hepatology University Hospital of Essen Essen, Germany

Innate immunity as a therapeutic target in IBD. Elke Cario Division of Gastroenterology & Hepatology University Hospital of Essen Essen, Germany Innate immunity as a therapeutic target in IBD Elke Cario Division of Gastroenterology & Hepatology University Hospital of Essen Essen, Germany The intestinal mucosa must rapidly recognize luminal pathogens

More information

Signal Transduction in Inflammatory Bowel Disease

Signal Transduction in Inflammatory Bowel Disease E v e n t s 0 6 4 Signal Transduction in Inflammatory Bowel Disease 0 1 2 3 4 1 0 1 0 1 0 1 0 1 0 F L 2 - H e ig h t Vineeta Khare Ph.D Overview Inflammatory Bowel Diseases 1. Epidemiology, Symptoms and

More information

Probiotic bacteria: mechanisms of action?

Probiotic bacteria: mechanisms of action? Probiotic bacteria: mechanisms of action? Probiotic derived antibacterial substances (microcins) Competitive inhibition of pathogens Modulation of inflammatory responses: Increasing antiinflammatory cytokine

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplemental Figure 1. Furin is efficiently deleted in CD4 + and CD8 + T cells. a, Western blot for furin and actin proteins in CD4cre-fur f/f and fur f/f Th1 cells. Wild-type and furin-deficient CD4 +

More information

Perinatal Nutrition. Disclosure Statement. Annual Meeting of the NASPGHAN. Keynote Lecture: Nutrients in the Perinatal Environment: Lessons Learned

Perinatal Nutrition. Disclosure Statement. Annual Meeting of the NASPGHAN. Keynote Lecture: Nutrients in the Perinatal Environment: Lessons Learned Annual Meeting of the NASPGHAN Chicago, ILL October 10-13, 2013 Keynote Lecture: Nutrients in the Perinatal Environment: Lessons Learned Allan Walker, M.D. Boston, MA Disclosure Statement Dr. Allan Walker

More information

Chronic Granulomatous Disease Managing GI Issues

Chronic Granulomatous Disease Managing GI Issues Chronic Granulomatous Disease Managing GI Issues N I C H O L A S H A R T O G, M D D i r e c t o r o f P e d i a t r i c / A d u l t P r i m a r y I m m u n o d e f i c i e n c y C l i n i c A s s i s t

More information

Inflammation in the clinic

Inflammation in the clinic Inflammation in the clinic Stephen T. Holgate MRC Clinical Professor of Immunopharmacology ILSI Europe Workshop, Seville, May 14-15 2012 The immune system acts in four general ways to ensure host defence

More information

Tpl2 ablation promotes intestinal inflammation and tumorigenesis in Apc min mice by inhibiting IL-10 secretion and regulatory T-cell generation

Tpl2 ablation promotes intestinal inflammation and tumorigenesis in Apc min mice by inhibiting IL-10 secretion and regulatory T-cell generation Tpl2 ablation promotes intestinal inflammation and tumorigenesis in Apc min mice by inhibiting IL-10 secretion and regulatory T-cell generation Oksana B. Serebrennikova a, Christos Tsatsanis a,b, Changchuin

More information

T Regulatory Cell and Body Tolerance

T Regulatory Cell and Body Tolerance Available online at www.scholarsresearchlibrary.com Scholars Research Library Der Pharmacia Lettre, 2017, 9 [5]:23-28 [http://scholarsresearchlibrary.com/archive.html] ISSN 0975-5071 USA CODEN: DPLEB4

More information

Micro-RNAs as regulators and possible diagnostic bio-markers in inflammatory bowel disease

Micro-RNAs as regulators and possible diagnostic bio-markers in inflammatory bowel disease Journal of Crohn's and Colitis (2011) 5, 520 524 available at www.sciencedirect.com REVIEW ARTICLE Micro-RNAs as regulators and possible diagnostic bio-markers in inflammatory bowel disease Paraskevi Archanioti

More information

Necrotizing Enterocolitis: The Role of the Immune System

Necrotizing Enterocolitis: The Role of the Immune System Necrotizing Enterocolitis: The Role of the Immune System Patricia Denning, M.D. Associate Professor in Pediatrics Division of Neonatology Emory University School of Medicine What is NEC? What is NEC? Necrotizing

More information

Intracellular MHC class II molecules promote TLR-triggered innate. immune responses by maintaining Btk activation

Intracellular MHC class II molecules promote TLR-triggered innate. immune responses by maintaining Btk activation Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining Btk activation Xingguang Liu, Zhenzhen Zhan, Dong Li, Li Xu, Feng Ma, Peng Zhang, Hangping Yao and Xuetao

More information

Use of extrapolation in small clinical trials:

Use of extrapolation in small clinical trials: Use of extrapolation in small clinical trials: Infliximab for pediatric ulcerative colitis Jessica J. Lee, MD, MMSc Medical Officer Division of Gastroenterology and Inborn Errors Products CDER/ FDA 1 Learning

More information

USCAP Pediatric Pathology Speciality Conference Case 3. S.Ranganathan, MD Children s Hospital of Pittsburgh of UPMC 4/13/2016

USCAP Pediatric Pathology Speciality Conference Case 3. S.Ranganathan, MD Children s Hospital of Pittsburgh of UPMC 4/13/2016 USCAP Pediatric Pathology Speciality Conference - 2016 SPP asks all individuals involved in the development and presentation of Continuing Medical Education (CME) activities to disclose all relationships

More information

MOLECULAR IMMUNOLOGY Manipulation of immune response Autoimmune diseases & the pathogenic mechanism

MOLECULAR IMMUNOLOGY Manipulation of immune response Autoimmune diseases & the pathogenic mechanism MOLECULAR IMMUNOLOGY Manipulation of immune response Autoimmune diseases & the pathogenic mechanism SCHMAIEL SHIRDEL CONTENT 2 Introduction Autoimmune diseases Classification Involved components Autoimmune

More information

The gut kidney axis in IgA nephropathy. Rosanna Coppo. Fondazione Ricerca Molinette Torino

The gut kidney axis in IgA nephropathy. Rosanna Coppo. Fondazione Ricerca Molinette Torino The gut kidney axis in IgA nephropathy Rosanna Coppo Turin, Italy Fondazione Ricerca Molinette Torino IgA nephropathy (IgAN): a disease originated from mucosal immunity dysregulation IgA: most prevalent

More information

Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured

Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured Supplemental Figure 1. Signature gene expression in in vitro differentiated Th0, Th1, Th2, Th17 and Treg cells. (A) Naïve CD4 + T cells were cultured under Th0, Th1, Th2, Th17, and Treg conditions. mrna

More information

Genetic and Environmental Risks for IBD

Genetic and Environmental Risks for IBD Genetic and Environmental Risks for IBD CCFA April 26, 2014 Presented by: Name goes here April 30, 2014 TheoTheodore 1 Genetic and Environmental Risks for IBD Theodore M. Bayless, M.D. Director Emeritus

More information

D CD8 T cell number (x10 6 )

D CD8 T cell number (x10 6 ) IFNγ Supplemental Figure 1. CD T cell number (x1 6 ) 18 15 1 9 6 3 CD CD T cells CD6L C CD5 CD T cells CD6L D CD8 T cell number (x1 6 ) 1 8 6 E CD CD8 T cells CD6L F Log(1)CFU/g Feces 1 8 6 p

More information

Autoimmune Diseases. Betsy Kirchner CNP The Cleveland Clinic

Autoimmune Diseases. Betsy Kirchner CNP The Cleveland Clinic Autoimmune Diseases Betsy Kirchner CNP The Cleveland Clinic Disclosures (financial) No relevant disclosures Learning Objectives Explain the pathophysiology of autoimmune disease Discuss safe administration

More information

The enteric microbiota: Implications for IBD. Eugene B. Chang, M.D. University of Chicago

The enteric microbiota: Implications for IBD. Eugene B. Chang, M.D. University of Chicago The enteric microbiota: Implications for IBD Eugene B. Chang, M.D. University of Chicago On a per cell basis, humans are mostly prokaryote 100 90 80 70 60 50 40 30 20 10 0 EuK ProK The microbial flora

More information

VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses. Li Wang. Dartmouth Medical School

VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses. Li Wang. Dartmouth Medical School VISTA, a novel immune checkpoint protein ligand that suppresses anti-tumor tumor T cell responses Li Wang Dartmouth Medical School The B7 Immunoglobulin Super-Family immune regulators APC T cell Co-stimulatory:

More information

ULCERATIVE COLITIS. Chronic inflammatory bleeding ulcers in the colonic mucosa of unknown etiology. Low rate of spontaneous remission.

ULCERATIVE COLITIS. Chronic inflammatory bleeding ulcers in the colonic mucosa of unknown etiology. Low rate of spontaneous remission. ULCERATIVE COLITIS Chronic inflammatory bleeding ulcers in the colonic mucosa of unknown etiology. No pathogen identified, contagious transmission never documented. Low rate of spontaneous remission. Lack

More information

XV Jornada de Avances en Hepatología Málaga 20 y 21 de Mayo de Barrera intestinal en la cirrosis. Agustín Albillos

XV Jornada de Avances en Hepatología Málaga 20 y 21 de Mayo de Barrera intestinal en la cirrosis. Agustín Albillos XV Jornada de Avances en Hepatología Málaga 20 y 21 de Mayo de 2016 Barrera intestinal en la cirrosis Agustín Albillos Hospital Universitario Ramón y Cajal Universidad de Alcalá, Ciberehd Madrid, Spain

More information

A crucial role for HVEM and BTLA in preventing intestinal inflammation

A crucial role for HVEM and BTLA in preventing intestinal inflammation Washington University School of Medicine Digital Commons@Becker Open Access Publications 2008 A crucial role for HVEM and BTLA in preventing intestinal inflammation Marcos W. Steinberg La Jolla Institute

More information

Autoimmune diseases, their pathogenic mechanisms and treatment of unwanted immune responses (Janeway s Immunobiology)

Autoimmune diseases, their pathogenic mechanisms and treatment of unwanted immune responses (Janeway s Immunobiology) Autoimmune diseases, their pathogenic mechanisms and treatment of unwanted immune responses (Janeway s Immunobiology) Picture source: https://www.klini kum.uniheidelberg.de/fil eadmin/pressest elle/pm_neu/20

More information

Inflammatory Bowel Diseases (IBD) Clinical aspects Nitsan Maharshak M.D., IBD Center, Department of Gastroenterology and Liver Diseases Tel Aviv Soura

Inflammatory Bowel Diseases (IBD) Clinical aspects Nitsan Maharshak M.D., IBD Center, Department of Gastroenterology and Liver Diseases Tel Aviv Soura Inflammatory Bowel Diseases (IBD) Clinical aspects Nitsan Maharshak M.D., IBD Center, Department of Gastroenterology and Liver Diseases Tel Aviv Sourasky Medical Center Tel Aviv, Israel IBD- clinical features

More information

A Case of Crohn s Disease with Mesalazine Allergy that was Difficult to Differentiate from Comorbid Ulcerative Colitis

A Case of Crohn s Disease with Mesalazine Allergy that was Difficult to Differentiate from Comorbid Ulcerative Colitis doi: 10.2169/internalmedicine.1607-18 http://internmed.jp CASE REPORT A Case of Crohn s Disease with Mesalazine Allergy that was Difficult to Differentiate from Comorbid Ulcerative Colitis Rumiko Tsuboi,

More information

How to differentiate Segmental Colitis Associated with Diverticulosis and Inflammatory Bowel Diseases?

How to differentiate Segmental Colitis Associated with Diverticulosis and Inflammatory Bowel Diseases? How to differentiate Segmental Colitis Associated with Diverticulosis and Inflammatory Bowel Diseases? Alessandro Armuzzi Lead IBD Unit Complesso Integrato Columbus Fondazione Policlinico Gemelli Università

More information

INTERNATIONAL COURSE ON THE PATHOLOGY OF THE DIGESTIVE SYSTEM VICTOR BABES NATIONAL INSTITUTE OF PATHOLOGY BUCHAREST 7-8 BUCHAREST 2014

INTERNATIONAL COURSE ON THE PATHOLOGY OF THE DIGESTIVE SYSTEM VICTOR BABES NATIONAL INSTITUTE OF PATHOLOGY BUCHAREST 7-8 BUCHAREST 2014 INTERNATIONAL COURSE ON THE PATHOLOGY OF THE DIGESTIVE SYSTEM VICTOR BABES NATIONAL INSTITUTE OF PATHOLOGY BUCHAREST 7-8 BUCHAREST 2014 Endoscopic biopsy samples of naïve colitides patients: Role of basal

More information

Immune response to infection

Immune response to infection Immune response to infection Dr. Sandra Nitsche (Sandra.Nitsche@rub.de ) 20.06.2018 1 Course of acute infection Typical acute infection that is cleared by an adaptive immune reaction 1. invasion of pathogen

More information

Role of Th17 cells in the immunopathogenesis of dry eye disease

Role of Th17 cells in the immunopathogenesis of dry eye disease Role of Th17 cells in the immunopathogenesis of dry eye disease The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Chauhan,

More information