Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 15, Issue 6, Pages 1555-1567Publisher
WILEY
DOI: 10.1111/ajt.13140
Keywords
ELEM: KEYWORD PBYR: 2015 ITEM: 014 SEQN: 4 EMSG: AUTHOR_KEYWORD MISC18 Found colon in the keyword tolerance: mechanisms
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Funding
- National Health and Medical Research Council of Australia [512489, 1029601]
- National Health
- Medical Research Council Postgraduate Scholarship
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IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of inflammatory and autoimmune diseases. However the role of IL-17 in renal allograft rejection has not been fully explored. Here, we investigate the impact of IL-17 in a fully MHC-mismatched, life-sustaining, murine model of kidney allograft rejection using IL-17 deficient donors and recipients (IL-17(-/-) allografts). IL-17(-/-) allografts exhibited prolonged survival which was associated with reduced expression of the Th1 cytokine IFN- and histological attenuation of acute and chronic allograft rejection, as compared to wild-type allograft recipients. Results were confirmed in WT allograft recipients treated with an IL-17 blocking antibody. Subsequent experiments using either donors or recipients deficient in IL-17 showed a trend towards prolongation of survival only when recipients were IL-17(-/-). Administration of a depleting anti-CD25 antibody to IL-17(-/-) recipients abrogated the survival advantage conferred by IL-17 deficiency, suggesting the involvement of a CD4(+)CD25(+) T cell regulatory mechanism. Therefore, IL-17 deficiency or neutralization was protective against the development of kidney allograft rejection, which may be mediated by impairment of Th1 responses and/or enhanced protection by Tregs.
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