Th17 Pathway Research By Bio-Plex
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1 Th17 Pathway Research By Bio-Plex Zhiyang Shen, Senior Product Manager Bio-Rad Laboratories, Inc 2011 年 6 月 28 日星期二
2 T helper cell research Timeline: advances on T helper research. Figure depicts some of the most relevant findings in the field of T helper research Alexandre S Basso et al. Cell Research, Vol 19 No 4, April 2009
3 Th17 Cytokine Pathway The Th17 Cytokine Pathway is au current The importance of the Th17 cytokine pathway in many diseases is a recent discovery (in the last 5 years). Researchers are studying this group of cytokines to understand immune system function in numerous diseases, especially autoimmune diseases, as summarized in the adjacent table. The Th17 pathway is also a new area of focus for the study of the body s response to other inflammatory conditions such as those arising from conditions noted in the table. Lupus Th17 pathway implicated in Disease States, especially Autoimmune Diseases Rheumatoid Arthritis (RA) Multiple Sclerosis (MS) Psoriasis Lung Disease Crohn s Disease Diabetes (Type 1) Th17 pathway implicated in response to Inflammatory Conditions related to: Smoking Organ/tissue Transplantation Rejection Bacterial Infection Viral Infection Parasitic Infection HIV Status Cardiovascular Disease Traumatic Injury
4 Th17 Cytokine Pathway What is a Th17 cell? Th17 cells are a subclass of immune cells called T helper (Th) cells, which are a type of white blood cell whose specific immunological purpose is to directing the function of other immune cell types. Th17 cells are identified by the major cytokine they release: IL-17. Steps in the generation of Th17 cells. The activation of naïve T cells in the presence of TGF-b and IL-6 initiates the Th17 differentiation pathway. Amit Awasthi and Vijay K. Kuchroo,International Immunology, Vol. 21, No. 5, pp
5 Th17 Pathway Coverage Th17 Pathway Coverage Some cytokines regulate theproductionand function of Th17 cells (positive and negative regulators) Others are released by Th17 cellsupon activation. Others are further downstreamin the Th17 pathway. The adjacent image shows the complex interactions of cytokines with the Th17 cell (center), and the release of cytokines from the cell. Typical symptoms: skin inflammation and even canker
6 Importance of Th17 pathway in Today s Research A quick internet search reveals the recent explosion in the study of Th17 cytokines. Multiple Sclerosis March 2011 YTD Google Scholar citations on Th17 cytokine : >17,500 Percentage of those citations from last 3 years: 85% Prominent research topics are represented on this slide. Rheumatoid Arthritis Crohn s Disease Bacterial Infection
7 Some scientists concerns on Th17 cell Causes of activation of Th17 cell are under debating, especially the role of TGF-β1in Human What is the actual role of transcription factor RORγt in the development of Th17 cell? And can it be developed to a therapeutic target? The Role of Treg and its mechanism Distinct or overlay roles of IL-17A and IL-17F? Any changes of Th17 pathway in various diseases. Can we discover some biomarkers or targets for diagnostic and therapeutic applications from differentiation between controls and some specific diseases. Th17 cell signaling transduction in various diseases. Is there any biomarkers or targets in cell signaling pathway? Profiling cytokines in Th17 cell Discover mechanism, Find biomarkers and targets
8 Some scientists concerns on Th17 cell Th17 cytokine biology in mouse and human: Tesmer et al Role of IL-17 in human immune responses
9 Some scientists concerns on Th17 cell Although the Th1/Th2 paradigm represented a strong experimental and theoretical basis allowing significant advances in the immunology field, it was proven insufficient to fully explain certain immunological phenomena. However, we should not expect that adding one or two new T-cell subsets will give us a complete picture. Rather a lot more layers of complexity will be necessary to uncover the ways the adaptive immune system swings between tolerance and effector responses. For Th17 cell, it also needs strong and proven experimental and theoretical basis for mechanism discovery and medical applications.
10 TH-17 cells, like Treg cells, can be selected by self antigens in the thymus.
11 Differential roles of IL-17A and IL-17F
12 Th17 pathway and cancer Miyahara et al. PNAS October 7, 2008 vol. 105 no
13 Th17 pathway and cancer Despite recent advances in our understanding of the differentiation and function of Th17 cells in humans, very little is known about their prevalence and regulation in human cancer. Here, we report the presence of high percentages of Th17 cells that secrete predominantly IL-17 in the ovarian cancer-infiltrating T cell population. Cytokine profile analysis revealed that tumor cells, tumor-derived fibroblasts, and antigen presenting cells (APCs) secrete several key cytokines in the tumor microenvironment. We found that IL-1 was a potent inducer of Th17 cell differentiation and expansion, whereas IL-6 and IL-23 were capable of expanding memory Th17 cells. Here, we provide an insightful mechanism by which Th17 cells are generated and regulated by cytokines secreted from tumor cells and their immune infiltrates. Miyahara et al. PNAS October 7, 2008 vol. 105 no
14 Cytokine Profiling for asthma predictors
15 Bio-Plex Pro mouse Th17 Panel Bio-Plex Pro mouse Th17 panel Th17 pathway Panel A, Group I (6-plex) Panel B, Group III (8-plex) Singleplex Assays, Group III TGF-β Assays IL-6 IL-17F IL-25 (IL-17E) TGF- β1 IL-17A IL-23 IL-27p28 TGF- β2 IL-10 IL-21 ICAM-1 TGF- β3 IFN-γ IL-22 TNF-α MIP-3α IL-1β CD40L IL-33 IL-31
16 Bio-Plex Pro mouse Th17 Panel Validation data of Bio-Plex Pro mouse Th17 Panel
17 Bio-Plex Pro mouse Th17 Panel Assay performance Optimized assay working ranges to measure cytokines from normal and diseased samples LODs are quite low, indicating very sensitive assays. Extremely precise assays, as indicated by low % Coefficient of Variation (%CV)
18 Bio-Plex Pro mouse Th17 Panel Validation data of Bio-Plex Pro mouse Th17 Panel
19 Order information Bio-Plex Pro mouse Th17 Panel
20 On behalf of the Bio-Rad s Bio-PlexTeam, thank you for your attention.
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