Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression

被引:1749
作者
Lord, GM
Matarese, G
Howard, LK
Baker, RJ
Bloom, SR
Lechler, RI
机构
[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, Dept Immunol, London W12 0NN, England
[2] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Sch Med, Dept Endocrinol, London W12 0NN, England
关键词
D O I
10.1038/29795
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Nutritional deprivation suppresses immune function(1-3). The cloning of the obese gene and identification of its protein product leptin(4) has provided fundamental insight into the hypothalamic regulation of body weight(5,6). Circulating levels of this adipocyte-derived hormone are proportional to fat mass(6,7) but maybe lowered rapidly by fasting(8,9) or increased by inflammatory mediators(10,11). The impaired T-cell immunity of mice(12,13) now known to be defective in leptin (ob/ob)(4) or its receptor (db/db)(14,13), has never been explained. Impaired cell-mediated immunity(1-3) and reduced levels of leptin(7) are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases(16). We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells. Leptin increased Th1 and suppressed Th2 cytokine production. Administration of leptin to mice reversed the immunosuppressive effects of acute starvation. Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.
引用
收藏
页码:897 / 901
页数:5
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