التفاصيل البيبلوغرافية
| العنوان: |
IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice. |
| المؤلفون: |
Rankin, Andrew L.1 Andrew.Rankin@pfizer.com, Guay, Heath1,2, Herber, Deborah1, Bertino, Sarah A.3, Duzanski, Tatyana A.1, Carrier, Yijun1, Keegan, Sean1, Senices, Mayra1, Stedman, Nancy4, Ryan, Mark1, Bloom, Laird5, Medley, Quintus1, Collins, Mary1, Nickerson-Nutter, Cheryl1, Craft, Joe3, Young, Deborah1, Dunussi-Joannopoulos, Kyri1 |
| المصدر: |
Journal of Immunology. 2/15/2012, Vol. 188 Issue 4, p1656-1667. 12p. |
| مصطلحات موضوعية: |
*CELL receptors, *LYMPHOCYTES, *LABORATORY mice, *CYTOKINES, *B cells, *T cells |
| مستخلص: |
MRL/MpJ-Faslpr/lpr/J (MRLlpr) 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 MRLlpr 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 MRLlpr mice deficient in IL-21R (MRLlpr.IL-21R-/-). Lymphadenopathy and splenomegaly, which are characteristic traits of the MRLlpr 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 MRLlpr mice. Correspondingly, we observed a significant reduction in autoantibody titers. Activated CD4+ CD44+ CD62Llo 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-γ . T extrafollicular helper cells are a recently described subset of activated CD4+ T cells that function as the primary inducers of autoantibody production in MRLlpr 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 MRLlpr mice. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
