Dendritic cells can act as interpreters of the local microenvironment Hekla Sigmundsdóttir
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1 Dendritic cells can act as interpreters of the local microenvironment Hekla Sigmundsdóttir Stanford University, California.
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5 Homology between vitamin and vitamin D Vitamin Retinoic acid RR RR RXR α4β7 CCR9 Gut homing Vitamin D 1,25D3 VDR VDR RXR??? Skin homing
6 Based on these parallels, we hypothesized that sunlight-induced vitamin D3 might help program the migratory activity of skinassociated T cells.
7 1,25D3 induces the expression of on CD8+ T cells
8 FCS sorting of positive and negative subsets of T cells for microarray analysis CL CL++ CL ,25(OH) 2 D3 + IL-12 treated T cells (CD3+CD28 activated)
9 Genome-wide expression profiling of sorted T cell subsets and DCs Name of Gene CYP271 ffymetrix Systemic Name _at IL12 CL+ - T cells IL12+1,25D3 CL+ - CL Derived DC CYP2R _at _at 2691 CYP27B _at CYP _at 99 VDR _s_at RXRα _s_at RXRβ GPDH _at _x
10 25-Hydroxylases (CYP271, CYP2R1) 1-Hydroxylase (CYP27B1)
11 25-Hydroxylases (CYP271, CYP2R1) 1-Hydroxylase (CYP27B1)
12 25-Hydroxylases (CYP271, CYP2R1) 1-Hydroxylase (CYP27B1)
13 Genome-wide expression profiling of sorted T cell subsets and DCs D3 25(OH)D3 1,25(OH) 2 D3 Name of Gene CYP271 CYP27B1 CYP24 ffymetrix Systemic Name _at IL12 CL T cells IL12+1,25D3 CL+ - CL Derived DC CYP2R _at _at _at _at VDR _s_at RXRα _s_at RXRβ GPDH _at _x
14 1,25D3 induces the expression of on CD8+ T cells (% of positive response) ,25D Concentration (nm) 1,25(OH) 2 D3 VDR RXR
15 ctivated CD8+ T cells have a functional 1-hydroxylase (% of positive response) ,25D3 25D Concentration (nm) 25(OH)D3 1-hydroxylase 1,25(OH) 2 D3 VDR RXR
16 ctivated CD8+ T cells can convert 25D3 to 1,25D D3 1,25D3 (pm) Concentration (nm) 25(OH)D3 1-hydroxylase 1,25(OH) 2 D3 VDR RXR
17 CD8+ T cells do not have a functional 25-hydroxylase (% of positive response) ,25D3 25D3 D Concentration (nm) 25-hydroxylase 1-hydroxylase Vitamin D3 X 25(OH)D3 1,25(OH) 2 D3 VDR RXR
18 ctivated CD8+ T cells cannot convert D3 to 1,25D3 1,25D3 (pm) D3 D ,25D3 25D3 D Concentration (nm) Concentration (nm) 25-hydroxylase 1-hydroxylase Vitamin D3 X 25(OH)D3 1,25(OH) 2 D3 VDR RXR
19 Genome-wide expression profiling of sorted T cell subsets and DCs Name of Gene ffymetrix Systemic Name IL12 CL+ - T cells IL12+1,25D3 CL+ - CL+ + Derived DC D3 25(OH)D3 1,25(OH) 2 D3 CYP271 CYP27B1 CYP _at CYP2R _at _at _at _at VDR _s_at RXRα _s_at RXRβ GPDH _at _x
20 DCs have a functional 1-hydroxylase (% of positive response) D Concentration (nm) 1-hydroxylase 25(OH)D3 1,25(OH) 2 D3 VDR RXR
21 DCs have a functional 25-hydroxylase (% of positive response) D3 D Concentration (nm) 25-hydroxylase 1-hydroxylase Vitamin D3 25(OH)D3 1,25(OH) 2 D3 VDR RXR
22 DCs can convert D3 and 25D3 to 1,25D3 1,25D3 (pm ) D3 D Concentration (nm) D3 D Concentration (nm) 25-hydroxylase 1-hydroxylase Vitamin D3 25(OH)D3 1,25(OH) 2 D3 VDR RXR
23 Skin-exiting DCs are capable of converting D3 to 1,25D ,25D3 (pm) DCs Total cells
24 Dietary form of vitamin D (D2) is not as effective as the sunlight induced form (D3)
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27 1,25D3 can be added later and is still effective medium IL-12 1,25D3 IL-12+1,25D Day 6 CL CL CL CL Day 12 CL CL CL CL CL ,25D3 added on day 6 CD8+ T cells
28 1,25D3 can be added later and is still effective
29 1,25D3 can be added later and is still effective
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32 1,25D3 induces = dermis-epidermis = We still don t know what Induces this movement
33 cknowledgements Eugene Butcher Junliang Pan Dulce Soler, MLNM Gudrun Debes Carsten lt ida Habtezion Lusijah Rott Cathy Crumpton Funding NIH Stanford University DDC grant
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