| Autor: |
Jain, Shweta, Park, Giljun, Sproule, Thomas J., Christianson, Gregory J., Leeth, Caroline M., Wang, Hongsheng, Roopenian, Derry C., IIIMorse, Herbert C. |
| Předmět: |
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| Zdroj: |
PLoS ONE; 4/6/2016, Vol. 11 Issue 4, p1-19, 19p |
| Abstrakt: |
IL6 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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