title: Deficient leptin signaling ameliorates systemic lupus erythematosus lesions in MRL/Mp-Fas lpr mice.
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.
authors.affiliation: Department of Hematology and Immunology, Kanazawa Medical University, Uchinada, Kahoku-gun, Ishikawa 920-0293, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Fujita
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.forename: Tomomi
authors.initials: T
authors.lastname: Sato
authors.forename: Takuji
authors.initials: T
authors.lastname: Nakamura
authors.forename: Haruka
authors.initials: H
authors.lastname: Iwao
authors.forename: Akio
authors.initials: A
authors.lastname: Nakajima
authors.forename: Miyuki
authors.initials: M
authors.lastname: Miki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sakai
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kawanami
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Masaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Fukushima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Okazaki
authors.forename: Hisanori
authors.initials: H
authors.lastname: Umehara
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D020738:Leptin / Q000172:deficiency* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018655:Lymphocyte Count; D008297:Male; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008820:Mice, Obese; D012217:Rheumatoid Factor / Q000097:blood; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly / Q000209:etiology / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D001324:Autoantigens; D007074:Immunoglobulin G; D020738:Leptin; D004247:DNA; D012217:Rheumatoid Factor