{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:56:09Z","timestamp":1791064569233,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,2,3]]},"abstract":"<jats:p>\n                    Interleukin 21 (IL-21) is a pleiotropic cytokine produced by CD4 T cells that affects the differentiation and function of T, B, and NK cells by binding to a receptor consisting of the common cytokine receptor \u03b3 chain and the IL-21 receptor (IL-21R). IL-21, a product associated with IL-17-producing CD4 T cells (T\n                    <jats:sub>H<\/jats:sub>\n                    17) and follicular CD4 T helper cells (T\n                    <jats:sub>FH<\/jats:sub>\n                    ), has been implicated in autoimmune disorders including the severe systemic lupus erythematosus (SLE)-like disease characteristic of BXSB-\n                    <jats:italic>Yaa<\/jats:italic>\n                    mice. To determine whether IL-21 plays a significant role in this disease, we compared IL-21R-deficient and -competent BXSB-\n                    <jats:italic>Yaa<\/jats:italic>\n                    mice for multiple parameters of SLE. The deficient mice showed none of the abnormalities characteristic of SLE in IL-21R-competent\n                    <jats:italic>Yaa<\/jats:italic>\n                    mice, including hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal zone B cells and monocytosis, renal disease, and premature morbidity. IL-21 production associated with this autoimmune disease was not a product of T\n                    <jats:sub>H<\/jats:sub>\n                    17 cells and was not limited to conventional CXCR5\n                    <jats:sup>+<\/jats:sup>\n                    T\n                    <jats:sub>FH<\/jats:sub>\n                    but instead was produced broadly by ICOS\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    splenic T cells. IL-21 arising from an abnormal population of CD4 T cells is thus central to the development of this lethal disease, and, more generally, could play an important role in human SLE and related autoimmune disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0807309106","type":"journal-article","created":{"date-parts":[[2009,1,21]],"date-time":"2009-01-21T21:40:22Z","timestamp":1232574022000},"page":"1518-1523","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":272,"title":["A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-\n                    <i>Yaa<\/i>\n                    mice"],"prefix":"10.1073","volume":"106","author":[{"given":"Jason A.","family":"Bubier","sequence":"first","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Sproule","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oded","family":"Foreman","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanne","family":"Spolski","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Shaffer","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Herbert C.","family":"Morse","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren J.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda MD 20892; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derry C.","family":"Roopenian","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780221105"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124978"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603912103"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040504"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090316"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.06.001"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090344"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05970"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05969"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1488"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041057"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5361"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.075424"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.533003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.159.2.629"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21365"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.4.2048"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.8.5236"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03555"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1714"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080840"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050632"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364424"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1423.063"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.6.3822"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22452"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1552"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072057"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838511"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838529"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7097"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.12.8180"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.7867"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830251231"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.5.1023"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.0170"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.4.2354"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06253"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.7.3528"},{"key":"e_1_3_3_41_2","doi-asserted-by":"crossref","first-page":"4932","DOI":"10.4049\/jimmunol.156.12.4932","article-title":"Beta2-microglobulin dependence of the lupus-like autoimmune syndrome of MRL-lpr mice","volume":"156","author":"Christianson GJ","year":"1996","unstructured":"GJ Christianson, et al., Beta2-microglobulin dependence of the lupus-like autoimmune syndrome of MRL-lpr mice. 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