Abstract
IL-17 is a pro-inflammatory cytokine implicated in the pathogenesis of glomerulonephritis and IL-17 deficient mice are protected from nephrotoxic nephritis. However, a regulatory role for IL-17 has recently emerged. We describe a novel protective function for IL-17 in the kidney. Bone marrow chimeras were created using wild-type and IL-17 deficient mice and nephrotoxic nephritis was induced. IL-17 deficient hosts transplanted with wild-type bone marrow had worse disease by all indices compared to wild-type to wild-type bone marrow transplants (serum urea p<0.05; glomerular thrombosis p<0.05; tubular damage p<0.01), suggesting that in wild-type mice, IL-17 production by renal cells resistant to radiation is protective. IL-17 deficient mice transplanted with wild-type bone marrow also had a comparatively altered renal phenotype, with significant differences in renal cytokines (IL-10 p<0.01; IL-1β p<0.001; IL-23 p<0.01), and macrophage phenotype (expression of mannose receptor p<0.05; inducible nitric oxide synthase p<0.001). Finally we show that renal mast cells are resistant to radiation and produce IL-17, suggesting they are potential local mediators of disease protection. This is a novel role for intrinsic cells in the kidney that are radio-resistant and produce IL-17 to mediate protection in nephrotoxic nephritis. This has clinical significance as IL-17 blockade is being trialled as a therapeutic strategy in some autoimmune diseases.
Highlights
IL-17 is a pro-inflammatory cytokine with varied roles in inflammation, host defence and autoimmunity [1, 2]
Through bone marrow transplantation experiments we assessed the relative contributions of IL-17 from haematopoietic and intrinsic cells to nephrotoxic nephritis (NTN), and conclude that (1) transfer of wildtype haematopoietic cells to IL-17 deficient mice restores disease susceptibility and (2) rather than local IL-17 production contributing to pathogenesis as might be expected, it plays a protective role
WT mice transplanted with IL-17 deficient bone marrow tended to have the mildest disease of the three experimental groups consistent with our observation that local IL-17 production may play a protective role
Summary
IL-17 is a pro-inflammatory cytokine with varied roles in inflammation, host defence and autoimmunity [1, 2]. PLOS ONE | DOI:10.1371/journal.pone.0136238 August 28, 2015
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