Contributions
Abstract: P1613
Type: LB Poster
Abstract Category: Late Breaking News
Th17 cells are a subset of CD4+ T cells with proinflammatory activity that play a critical role in the development of autoimmunity including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response gene to complement (RGC)-32 is a downstream target of TGF-β with proliferative and profibrotic effects. As a downstream target of TGF-β, we assessed whether RGC-32 plays any role in the differentiation of TGF-β dependent T helper cell subsets, Th17 and iTregs. To this end we examined wild type and RGC-32 knockout (KO) mice for the in vitro development of Th17 cells and Th17-mediated autoimmune disease EAE. Here, we report that RGC-32 is preferentially increased during Th17 cell differentiation. CD4+ T cells from RGC-32 KO mice failed to polarize normally to the Th17 lineage as they exhibit a significant reduction in the proportion of IL-17A+ CD4+ cells, a significant decrease in the amount of IL-17A mRNA expression and in the level of secreted IL-17A. Naive T cells from mice lacking RGC-32 are defective in Th17 but not Tregs, Th1 or Th2 differentiation. Furthermore, RGC-32-/- mice develop an attenuated EAE phenotype associated with decreased frequency of IL-17-producing T cells in central nervous system. Therefore, we assessed whether alterations in TGF-β signaling contribute to the defective Th17 polarization of RGC-32-/- CD4 T-cells. The defect in Th17 differentiation was associated with a reduction in RoRγt, IRF4, BATF and SMAD-2 activation. Collectively, our results identify a novel, proinflammatory role for RGC-32 through promoting Th17 differentiation and autoimmunity and identify RGC-32 as a potential therapeutic target in MS and other Th17 mediated diseases.
Disclosure: Alexandru Tatomir: nothing to disclose.
Violeta Rus: nothing to disclose.
Vinh Nguyen: nothing to disclose.
Dallas Boodhoo: nothing to disclose.
Armugam P. Mekala: nothing to disclose.
Cornelia Cudrici: nothing to disclose.
Tudor C. Badea: nothing to disclose.
Horea Rus: nothing to disclose.
Abstract: P1613
Type: LB Poster
Abstract Category: Late Breaking News
Th17 cells are a subset of CD4+ T cells with proinflammatory activity that play a critical role in the development of autoimmunity including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Response gene to complement (RGC)-32 is a downstream target of TGF-β with proliferative and profibrotic effects. As a downstream target of TGF-β, we assessed whether RGC-32 plays any role in the differentiation of TGF-β dependent T helper cell subsets, Th17 and iTregs. To this end we examined wild type and RGC-32 knockout (KO) mice for the in vitro development of Th17 cells and Th17-mediated autoimmune disease EAE. Here, we report that RGC-32 is preferentially increased during Th17 cell differentiation. CD4+ T cells from RGC-32 KO mice failed to polarize normally to the Th17 lineage as they exhibit a significant reduction in the proportion of IL-17A+ CD4+ cells, a significant decrease in the amount of IL-17A mRNA expression and in the level of secreted IL-17A. Naive T cells from mice lacking RGC-32 are defective in Th17 but not Tregs, Th1 or Th2 differentiation. Furthermore, RGC-32-/- mice develop an attenuated EAE phenotype associated with decreased frequency of IL-17-producing T cells in central nervous system. Therefore, we assessed whether alterations in TGF-β signaling contribute to the defective Th17 polarization of RGC-32-/- CD4 T-cells. The defect in Th17 differentiation was associated with a reduction in RoRγt, IRF4, BATF and SMAD-2 activation. Collectively, our results identify a novel, proinflammatory role for RGC-32 through promoting Th17 differentiation and autoimmunity and identify RGC-32 as a potential therapeutic target in MS and other Th17 mediated diseases.
Disclosure: Alexandru Tatomir: nothing to disclose.
Violeta Rus: nothing to disclose.
Vinh Nguyen: nothing to disclose.
Dallas Boodhoo: nothing to disclose.
Armugam P. Mekala: nothing to disclose.
Cornelia Cudrici: nothing to disclose.
Tudor C. Badea: nothing to disclose.
Horea Rus: nothing to disclose.