Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Mice

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Jain , S , Park , G , Sproule , T J , Christianson , G J , Leeth , C M , Wang , H , Roopenian , D C & Morse , H C 2016 , ' Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Mice ' , PLoS One , vol. 11 , no. 4 , 0153059 . https://doi.org/10.1371/journal.pone.0153059

Title: Interleukin 6 Accelerates Mortality by Promoting the Progression of the Systemic Lupus Erythematosus-Like Disease of BXSB. Yaa Mice
Author: Jain, Shweta; Park, Giljun; Sproule, Thomas J.; Christianson, Gregory J.; Leeth, Caroline M.; Wang, Hongsheng; Roopenian, Derry C.; Morse, Herbert C.
Contributor: University of Helsinki, Clinicum
Date: 2016-04-06
Language: eng
Number of pages: 19
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/161516
Abstract: 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 T-FH 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 T-FH 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 T-FH in a signaling sequence that drives the lethal autoimmune disease of BXSB. Yaa mice.
Subject: CD4(+) T-CELLS
TOLL-LIKE RECEPTORS
ACTIVATE B-CELLS
MURINE LUPUS
ANTI-DNA
IN-VIVO
IL-6
TLR7
DIFFERENTIATION
EXPRESSION
3111 Biomedicine
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