IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL/MpJ-Faslpr/lpr/J Mice
| Autor: | Quintus G. Medley, Joe Craft, Heath Guay, Mayra Senices, Deborah Herber, Sarah A. Bertino, Sean Keegan, Tatyana A. Duzanski, Andrew L. Rankin, Nancy Stedman, Mark Ryan, Deborah Young, Laird Bloom, Kyri Dunussi-Joannopoulos, Yijun Carrier, Cheryl Nickerson-Nutter, Mary Collins |
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| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Mice Inbred MRL lpr Lymphocyte Cellular differentiation medicine.medical_treatment T cell Immunology Autoimmunity Context (language use) Plasma cell Lymphocyte Activation urologic and male genital diseases medicine.disease_cause Article Interferon-gamma Mice T-Lymphocyte Subsets immune system diseases medicine Animals Lupus Erythematosus Systemic Immunology and Allergy skin and connective tissue diseases Lymphatic Diseases Autoantibodies Skin Mice Knockout B-Lymphocytes Chemistry Interleukins Germinal center Cell Differentiation T-Lymphocytes Helper-Inducer medicine.anatomical_structure Cytokine Splenomegaly Receptors Interleukin-21 |
| Zdroj: | The Journal of Immunology. 188:1656-1667 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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