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Local IL-17 Production Exerts a Protective Role in Murine Experimental Glomerulonephritis.

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-1? 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.

SUBMITTER: Hamour S

PROVIDER: S-EPMC4552867 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Local IL-17 Production Exerts a Protective Role in Murine Experimental Glomerulonephritis.

Hamour Sally S Gan Poh-Yi PY Pepper Ruth R Florez Barros Fernanda F Wang Hsu-Han HH O'Sullivan Kim K Iwakura Yoichiro Y Cook Terence T Pusey Charles C Holdsworth Stephen S Salama Alan A

PloS one 20150828 8

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 t ...[more]

PMID: 26317864

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Dataset Information

Local IL-17 Production Exerts a Protective Role in Murine Experimental Glomerulonephritis.

Publications

Local IL-17 Production Exerts a Protective Role in Murine Experimental Glomerulonephritis.

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