Jain, ShwetaPark, GiljunSproule, Thomas J.Christianson, Gregory J.Leeth, Caroline M.Wang, HongshengRoopenian, Derry C.Morse, Herbert C. III2017-07-282017-07-282016-04-061932-6203http://hdl.handle.net/10919/78464IL6 is a multifunctional cytokine that drives terminal B cell differentiation and secretion of immunoglobulins. IL6 also cooperates with IL21 to promote differentiation of CD4+ T follicular helper cells (TFH). Elevated serum levels of IL6 correlate with disease flares in patients with systemic lupus erythematosus (SLE). We previously reported that IL21 produced by TFH plays a critical role in the development of the SLE-like disease of BXSB.Yaa mice. To examine the possible contributions of IL6 to disease, we compared disease parameters in IL6-deficient and IL6-competent BXSB.Yaa mice. We report that survival of IL6-deficient BXSB.Yaa mice was significantly prolonged in association with significant reductions in a variety of autoimmune manifestations. Moreover, B cells stimulated by co-engagement of TLR7 and B cell receptor (BCR) produced high levels of IL6 that was further augmented by stimulation with Type I interferon (IFN1). Importantly, the frequencies of TFH and serum levels of IL21 were significantly reduced in IL6-deficient mice. These findings suggest that high-level production of IL6 by B cells induced by integrated signaling from the IFN1 receptor, TLR7 and BCR promotes the differentiation of IL21-secreting TFH in a signaling sequence that drives the lethal autoimmune disease of BXSB.Yaa mice.? - ? (19) page(s)application/pdfenCreative Commons CC0 1.0 Universal Public Domain Dedicationcd4(+) t-cellstoll-like receptorsactivate b-cellsmurine lupusanti-dnain-vivoil-6tlr7differentiationexpressionArticle - Refereedhttps://doi.org/10.1371/journal.pone.0153059114Leeth, CM [0000-0002-5909-7623]