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Title: | Signal transducer and activation of transcription 6 (STAT6) regulates T helper type 1 (Th1) and Th17 nephritogenic immunity in experimental crescentic glomerulonephritis. | Authors: | Dewage L.;Kitching A.R. ;Holdsworth S.R. ;Summers S.A.;Phoon R.K.S.;Odobasic D. | Institution: | (Summers, Phoon, Odobasic, Dewage, Kitching, Holdsworth) Centre for Inflammatory Diseases, Monash University, Department of Medicine, Australia (Summers, Kitching, Holdsworth) Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia | Issue Date: | 8-Oct-2012 | Copyright year: | 2011 | Publisher: | Blackwell Publishing Ltd (9600 Garsington Road, Oxford OX4 2XG, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Clinical and Experimental Immunology. 166 (2) (pp 227-234), 2011. Date of Publication: November 2011. | Abstract: | 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. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1111/j.1365-2249.2011.04437.x | PubMed URL: | 21985369 [http://www.ncbi.nlm.nih.gov/pubmed/?term=21985369] | ISSN: | 0009-9104 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/30340 | Type: | Article |
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