Deficient Leptin Signaling Ameliorates Systemic Lupus Erythematosus Lesions in MRL/Mp-Fas Lpr Mice

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2014 Jan 7

PMID 24391210

Citations 22

Authors

Yoshimasa Fujita

Takao Fujii

Tsuneyo Mimori

Tomomi Sato

Takuji Nakamura

Haruka Iwao

Akio Nakajima

Miyuki Miki

Tomoyuki Sakai

Takafumi Kawanami

Masao Tanaka

Yasufumi Masaki

Toshihiro Fukushima

Toshiro Okazaki

Hisanori Umehara

Affiliations

Soon will be listed here.

Abstract

Leptin is secreted by adipocytes, the placenta, and the stomach. It not only controls appetite through leptin receptors in the hypothalamus, it also regulates immunity. In the current study, we produced leptin-deficient MRL/Mp-Fas(lpr) mice to investigate the potential role of leptin in autoimmunity. C57BL/6J-ob/ob mice were backcrossed with MRL/Mp-Fas(lpr) mice, which develop human systemic lupus erythematosus (SLE)-like lesions. The effects of leptin deficiency on various SLE-like manifestations were investigated in MRL/Mp-Fas(lpr) mice. The regulatory T cell population in the spleen was analyzed by flow cytometry, and the effects of leptin on regulatory T cells and Th17 cells were evaluated in vitro. Compared with leptin-producing MRL/Mp-Fas(lpr) mice, leptin-deficient MRL/Mp-Fas(lpr) mice showed less marked splenomegaly and a particularly low population of CD3(+)CD4(-)CD8(-)B220(+) T cells (lpr cells). Their serum concentrations of Abs to dsDNA were lower, and renal histological changes at age 20 wk were ameliorated. Regulatory T cells were increased in the spleens of leptin-deficient MRL/Mp-Fas(lpr) mice. Leptin suppressed regulatory T cells and enhanced Th17 cells in vitro. In conclusion, blockade of leptin signaling may be of therapeutic benefit in patients with SLE and other autoimmune diseases.

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