8.+Cytokines+1+slide

Wild type il 12 and il 23 share a p40 subunit and

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Unformatted text preview: h1 & Th17 EAE (MS mouse model) Discovery of Th17 cells Th17 model called experimental ens EAE:mous model mirror for MS IFN-γ-/- heterodimer receptor is a heterodimer Do you think IL-12 and IFN-γare the ONLY cytokines responsible for causing disease symptoms in EAE? Wild-type IL-12 and IL-23 share a p40 subunit and their receptors share the IL-12R beta1 subunit Discovery of Th17 cells Whit these data...what do you think is the cytokine cascade mediating disease in EAE notebook p35-/Wild-type p19+/- p40-/- & p19-/IFN-γ Autoimmune disease. What do Th17 are for? IL-17 Cytokine Transcription Environment Factor T helper Subsets IL-12 Naïve Tbet (STAT1) Th1 IL-4 & IL-5 GATA3 (STAT6) Th2 Th0 IL-6,IL-1beta, IL-23, TGF-Beta IL-6, IL-1β, IL-23, TGF-β ROR gamma t, ROR alpha RORγt, RORα Th17 Secrete Th1 IFN-γ Th2 IL-4, IL-5, IL-13 Th17 IL-17, IL-6, Chemokines Effects Cell Targets 1.  2.  3.  4.  5.  MΦ activation Phagocytosis MHC expression IgG2a CTL activation 1.  Eosinophilia 2.  Mast cell degranulation 3.  IgE, IgA 4.  Mucus secretion 1. Neutrophil 1.  Neutrophil 2. dampens Th2 response recruitment 2.  Inflammation CTLA4 on the T cell if it binds to B7 then it leads to cell cycle arrest instead of Cd28 TREG which has CD25 it takes up the IL2 B7.1 B7.2 Alegre, M et al Nat. Rev. Immunol. 2002 Mechanisms of Stopping Immune B7.1 Activation B7.2 Secrete Th1 IFN-γ Th2 IL-4, IL-5, IL-13 Th17 Treg IL-17, IL-6, Chemokines Effects Cell Targets 1.  2.  3.  4.  5.  MΦ activation Phagocytosis MHC expression IgG2a CTL activation 1.  Eosinophilia 2.  Mast cell degranulation 3.  IgE, IgA 4.  Mucus secretion 1.  Neutrophil recruitment 2.  Inflammation 1.  Prevents DC maturation 2.  Dampens T cell activity Cytokine Transcription Environment Factor T helper Subsets IL-12 Naïve Tbet (STAT1) Th1 IL-4 & IL-5 GATA3 (STAT6) Th2 Th0 IL-6, IL-1β, RORγt, IL-23, RORα TGF-β common TGF-beta TGF-β Th17 fox P3 FOXP3 TReg TGF beta is common a cell has low TGF Infection would increase TGF beta IL6 and IL23 both share TGF beta the tipping point between Treg or TH17 if you get IL6 and IL23 you get Th17 end The Treg/Th17 Balance The Treg/Th17 Balance TGF beta is a cytokine FoxP3 transcription factor. TGF-β IL-6, IL-1β, IL-23 TGF-β RORγt (RORα) STAT1, 3, 5 FoxP3 RA IL-23 IL-23R Tregs Th17 T helper cells and autoimmune disease ¨༊  Psoriasis ¤༊  Corticosteroids ¤༊  Retinoids (RA) ¤༊  Ustenikimab Th17 Treg Schmidt, et al Nat. Biotech. 2008 T helper cells and autoimmune disease ¨༊  Hygiene Hypothesis Ulcerative colitis and IBD Th17 Th2 Summary slide ¨༊  CD4 T helper subsets ¤༊  Th1, Th2, Th17 and Tregs ¤༊  Induced in the context of specific cytokine environments ¤༊  Their functions ¤༊  Cells they target ¨༊  Importance of inducing the differentiation of the appropriate subset in the context of disease...
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This document was uploaded on 03/10/2014 for the course BIOLOGY 104 at Tufts.

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