Heath Guay - Academia.edu (original) (raw)
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Papers by Heath Guay
The Journal of Immunology, 2012
MRL/MpJ-Fas lpr/lpr /J (MRL lpr ) mice develop lupus-like disease manifestations in an IL-21-depe... more MRL/MpJ-Fas lpr/lpr /J (MRL lpr ) mice develop lupus-like disease manifestations in an IL-21-dependent manner. IL-21 is a pleiotropic cytokine that can influence the activation, differentiation, and expansion of B and T cell effector subsets. Notably, autoreactive CD4 + T and B cells spontaneously accumulate in MRL lpr mice and mediate disease pathogenesis. We sought to identify the particular lymphocyte effector subsets regulated by IL-21 in the context of systemic autoimmunity and, thus, generated MRL lpr mice deficient in IL-21R (MRL lpr .IL-21R 2/2 ). Lymphadenopathy and splenomegaly, which are characteristic traits of the MRL lpr model were significantly reduced in the absence of IL-21R, suggesting that immune activation was likewise decreased. Indeed, spontaneous germinal center formation and plasma cell accumulation were absent in IL-21R-deficient MRL lpr mice. Correspondingly, we observed a significant reduction in autoantibody titers. Activated CD4 + CD44 + CD62L lo T cells also failed to accumulate, and CD4 + Th cell differentiation was impaired, as evidenced by a significant reduction in CD4 + T cells that produced the pronephritogenic cytokine IFN-g. T extrafollicular helper cells are a recently described subset of activated CD4 + T cells that function as the primary inducers of autoantibody production in MRL lpr mice. Importantly, we demonstrated that T extrafollicular helper cells are dependent on IL-21R for their generation. Together, our data highlighted the novel observation that IL-21 is a critical regulator of multiple pathogenic B and T cell effector subsets in MRL lpr mice.
The Journal of Immunology, 2012
MRL/MpJ-Fas lpr/lpr /J (MRL lpr ) mice develop lupus-like disease manifestations in an IL-21-depe... more MRL/MpJ-Fas lpr/lpr /J (MRL lpr ) mice develop lupus-like disease manifestations in an IL-21-dependent manner. IL-21 is a pleiotropic cytokine that can influence the activation, differentiation, and expansion of B and T cell effector subsets. Notably, autoreactive CD4 + T and B cells spontaneously accumulate in MRL lpr mice and mediate disease pathogenesis. We sought to identify the particular lymphocyte effector subsets regulated by IL-21 in the context of systemic autoimmunity and, thus, generated MRL lpr mice deficient in IL-21R (MRL lpr .IL-21R 2/2 ). Lymphadenopathy and splenomegaly, which are characteristic traits of the MRL lpr model were significantly reduced in the absence of IL-21R, suggesting that immune activation was likewise decreased. Indeed, spontaneous germinal center formation and plasma cell accumulation were absent in IL-21R-deficient MRL lpr mice. Correspondingly, we observed a significant reduction in autoantibody titers. Activated CD4 + CD44 + CD62L lo T cells also failed to accumulate, and CD4 + Th cell differentiation was impaired, as evidenced by a significant reduction in CD4 + T cells that produced the pronephritogenic cytokine IFN-g. T extrafollicular helper cells are a recently described subset of activated CD4 + T cells that function as the primary inducers of autoantibody production in MRL lpr mice. Importantly, we demonstrated that T extrafollicular helper cells are dependent on IL-21R for their generation. Together, our data highlighted the novel observation that IL-21 is a critical regulator of multiple pathogenic B and T cell effector subsets in MRL lpr mice.