title: Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis.
abstract: Leptin is produced almost exclusively by adipocytes and regulates body weight at the hypothalamic level. In addition, recent studies showed that leptin plays an important role in T lymphocyte responses. To examine the role of leptin in Ag-induced arthritis, the development of joint inflammation was assessed in immunized leptin-deficient mice (ob/ob), +/?, and wild-type mice (+/+) following the administration of methylated BSA into the knees. The results showed that ob/ob mice developed less severe arthritis compared with control mice. The levels of IL-1beta and TNF-alpha mRNA in the synovium of arthritic knees were lower in ob/ob than in +/? mice. In vitro Ag-specific T cell proliferative responses were significantly decreased in ob/ob mice with lower IFN-gamma and higher IL-10 production, suggesting a shift toward a Th2-type response in ob/ob mice. The serum levels of anti-methylated BSA Abs of any isotype were significantly decreased in arthritic ob/ob mice compared with controls. Essentially identical results were obtained in db/db mice, which lack the expression of the long isoform of leptin receptor. By RT-PCR, we observed that B lymphocytes express leptin receptor mRNA, indicating that in addition to its effect on the cellular response, leptin may exert a direct effect on B cell function. In conclusion, leptin contributes to the mechanisms of joint inflammation in Ag-induced arthritis by regulating both humoral and cell-mediated immune responses.
authors.affiliation: Laboratory of Rheumatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.forename: Alexander
authors.initials: A
authors.lastname: So
authors.forename: Véronique
authors.initials: V
authors.lastname: Chobaz-Péclat
authors.forename: Carole
authors.initials: C
authors.lastname: Morard
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martinez-Soria
authors.forename: Dominique
authors.initials: D
authors.lastname: Talabot-Ayer
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics*; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D001402:B-Lymphocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020738:Leptin / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D007375:Interleukin-1; D020738:Leptin; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D014409:Tumor Necrosis Factor-alpha; C515447:leptin receptor, mouse