Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis

Kei Goto, Yoshikatsu Kaneko, Yuya Sato, Tadashi Otsuka, Suguru Yamamoto, Shin Goto, Keiko Yamamoto, Tadashi Yamamoto, Hiroshi Kawachi, Michael P. Madaio, Ichiei Narita

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/ IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). Sheep NTS was administered in wild-type C57BL/6J mice and food-restricted, leptin-deficient C57BL/6J-ob/ob (FR-ob/ob) mice after preimmunization with sheep IgG. The profile of mRNA expression relevant to T helper lymphocytes in the kidneys was analyzed by quantitative realtime PCR (qRT-PCR). Cultured murine glomerular podocytes and peritoneal exudate macrophages (PEMs) were used to investigate the direct effect of leptin on IL-23 or MCP-1 production by qRT-PCR. Kidney injury and macrophage infiltration were significantly attenuated in FR-ob/ob mice 7 days after NTS injection. The Th17-dependent secondary immune response against deposited NTS in the glomeruli was totally impaired in FR-ob/ob mice because of deteriorated IL-17 and proinflammatory cytokine production including IL-23 and MCP-1 in the kidney. IL-23 was produced in glomerular podocytes in NTN mice and cultured murine glomerular podocytes produced IL-23 under leptin stimulation. MCP-1 production in PEMs was also promoted by leptin. Induction of MCP-1 expression was observed in PEMs regardless of Ob-Rb, and the leptin signal was transduced without STAT3 phosphorylation in PEMs. Leptin deficiency impairs the secondary immune response against NTS and down-regulates IL-23 production and Th17 responses in the NTN kidney, which is accompanied by decreased MCP-1 production and macrophage infiltration in the NTN kidney.

Original languageEnglish (US)
Pages (from-to)197-208
Number of pages12
JournalInternational Immunology
Volume28
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • CCL2
  • IL-17
  • IL-22
  • Ob-R
  • T17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Goto, K., Kaneko, Y., Sato, Y., Otsuka, T., Yamamoto, S., Goto, S., Yamamoto, K., Yamamoto, T., Kawachi, H., Madaio, M. P., & Narita, I. (2016). Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis. International Immunology, 28(4), 197-208. https://doi.org/10.1093/intimm/dxv067