Leptin signaling deficiency impairs humoral and cellular immune responses and attenuates experimental arthritis.
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.
Busso
Nathalie
N
Laboratory of Rheumatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
So
Alexander
A
Chobaz-Péclat
Véronique
V
Morard
Carole
C
Martinez-Soria
Eduardo
E
Talabot-Ayer
Dominique
D
Gabay
Cem
C
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
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