{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:55:59Z","timestamp":1791064559819,"version":"4.1.0"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,2,1]],"date-time":"2012-02-01T00:00:00Z","timestamp":1328054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>MRL\/MpJ-Faslpr\/lpr\/J (MRLlpr) mice develop lupus-like disease manifestations in an IL-21\u2013dependent 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\u2212\/\u2212). 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\u2013deficient 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-\u03b3. 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1003871","type":"journal-article","created":{"date-parts":[[2012,1,10]],"date-time":"2012-01-10T01:42:27Z","timestamp":1326159747000},"page":"1656-1667","source":"Crossref","is-referenced-by-count":77,"title":["IL-21 Receptor Is Required for the Systemic Accumulation of Activated B and T Lymphocytes in MRL\/MpJ-Fas<i>lpr\/lpr<\/i>\/J Mice"],"prefix":"10.1093","volume":"188","author":[{"given":"Andrew L","family":"Rankin","sequence":"first","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heath","family":"Guay","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Herber","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A","family":"Bertino","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana A","family":"Duzanski","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Carrier","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Keegan","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra","family":"Senices","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Stedman","sequence":"additional","affiliation":[{"name":"Drug Safety and Metabolism, Pfizer Research , Andover, MA 01810"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ryan","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laird","family":"Bloom","sequence":"additional","affiliation":[{"name":"Global Biotherapeutics Technologies, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quintus","family":"Medley","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Collins","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Nickerson-Nutter","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Craft","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Young","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyri","family":"Dunussi-Joannopoulos","sequence":"additional","affiliation":[{"name":"Inflammation and Immunology, Pfizer Research , Cambridge, MA 02140"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,2,15]]},"reference":[{"key":"2025032409501944900_r1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev.iy.09.040191.001331","article-title":"Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease","volume":"9","author":"Cohen","year":"1991","journal-title":"Annu. 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