title: 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-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.
authors: UCL Centre for Nephrology, Royal Free Hospital, London, United Kingdom.
authors: Sally
authors: S
authors: Hamour
authors: Centre for Inflammatory diseases, Monash University, Melbourne, Australia.
authors: Poh-Yi
authors: PY
authors: Gan
authors: UCL Centre for Nephrology, Royal Free Hospital, London, United Kingdom.
authors: Ruth
authors: R
authors: Pepper
authors: UCL Centre for Nephrology, Royal Free Hospital, London, United Kingdom.
authors: Fernanda
authors: F
authors: Florez Barros
authors: UCL Centre for Nephrology, Royal Free Hospital, London, United Kingdom.
authors: Hsu-Han
authors: HH
authors: Wang
authors: Centre for Inflammatory diseases, Monash University, Melbourne, Australia.
authors: Kim
authors: K
authors: O'Sullivan
authors: Research Institute for Biomedical Sciences, Tokyo University of Science, Tokyo, Japan.
authors: Yoichiro
authors: Y
authors: Iwakura
authors: Centre for Inflammation and Complement Research, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Terence
authors: T
authors: Cook
authors: Renal Section, Department of Medicine, Imperial College London, London, United Kingdom.
authors: Charles
authors: C
authors: Pusey
authors: Centre for Inflammatory diseases, Monash University, Melbourne, Australia.
authors: Stephen
authors: S
authors: Holdsworth
authors: UCL Centre for Nephrology, Royal Free Hospital, London, United Kingdom.
authors: Alan
authors: A
authors: Salama
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D053759:Interleukin-23 / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011836:Radiation Tolerance
chemical_list: C556062:IL10 protein, mouse; C587672:IL1B protein, mouse; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D016753:Interleukin-10