期刊
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 166, 期 2, 页码 227-234出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2249.2011.04437.x
关键词
glomerulonephritis; renal immunology/disease; T cells
类别
资金
- National Health and Medical Research Council of Australia [334067, 519426, 284499]
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-gamma t (Ror gamma t), 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 Ror gamma 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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