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Signal transducer and activation of transcription 6 (STAT6) regulates T helper type 1 (Th1) and Th17 nephritogenic immunity in experimental crescentic glomerulonephritis.

Authors: Summers, SA  Phoon, RK  Odobasic, D  Dewage, L  Kitching, AR  Holdsworth, SR 
Citation: Summers SA, etal., Clin Exp Immunol. 2011 Nov;166(2):227-34. doi: 10.1111/j.1365-2249.2011.04437.x.
Pubmed: (View Article at PubMed) PMID:21985369
DOI: Full-text: DOI:10.1111/j.1365-2249.2011.04437.x

Experimental crescentic glomerulonephritis is driven by systemic cellular immune responses. A pathogenic role for T helper type 1 (Th1) and Th17 cells is well established. T-bet, a key transcription factor required for Th1 lineage commitment, and retinoic acid-related orphan receptor-gammat (Rorgammat), a key Th17 transcription factor, are required for full expression of disease. Similarly, several Th1- and Th17-associated cytokines have been implicated in disease augmentation. The role of Th2 cells in the disease is less clear, although Th2-associated cytokines, interleukin (IL)-4 and IL-10, are protective. We sought to determine the role of signal transducer and activation of transcription 6 (STAT6), a key regulator of Th2 responses, in experimental crescentic glomerulonephritis. Compared to wild-type mice, histological and functional renal injury was enhanced significantly in STAT6(-/-) mice 21 days after administration of sheep anti-mouse glomerular basement membrane globulin. Consistent with the enhanced renal injury, both Th1 and Th17 nephritogenic immune responses were increased in STAT6(-/-) mice. Conversely, production of IL-5, a key Th2-associated cytokine, was decreased significantly in STAT6(-/-) mice. Early in the disease process systemic mRNA expression of T-bet and Rorgamma was increased in STAT6(-/-) mice. We conclude that STAT6 is required for attenuation of Th1 and Th17 nephritogenic immune responses and protection from crescentic glomerulonephritis.


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RGD Object Information
RGD ID: 7243976
Created: 2013-05-21
Species: All species
Last Modified: 2013-05-21
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.