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

Author

Listed:
  • Graham M. Lord

    (Imperial College School of Medicine, The Hammersmith Hospital)

  • Giuseppe Matarese

    (Imperial College School of Medicine, The Hammersmith Hospital
    Università di Napoli “Federico II”)

  • Jane K. Howard

    (Imperial College School of Medicine, The Hammersmith Hospital)

  • Richard J. Baker

    (Imperial College School of Medicine, The Hammersmith Hospital)

  • Stephen R. Bloom

    (Imperial College School of Medicine, The Hammersmith Hospital)

  • Robert I. Lechler

    (Imperial College School of Medicine, The Hammersmith Hospital)

Abstract

Nutritional deprivation suppresses immune function1,2,3. The cloning of the obese gene and identification of its protein product leptin4 has provided fundamental insight into the hypothalamic regulation of body weight5,6. Circulating levels of this adipocyte-derived hormone are proportional to fat mass6,7 but may be lowered rapidly by fasting8,9 or increased by inflammatory mediators10,11. The impaired T-cell immunity of mice12,13 now known to be defective in leptin (ob/ob)4 or its receptor (db/db)14,15, has never been explained. Impaired cell-mediated immunity1,2,3 and reduced levels of leptin7 are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases16. 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.

Suggested Citation

  • Graham M. Lord & Giuseppe Matarese & Jane K. Howard & Richard J. Baker & Stephen R. Bloom & Robert I. Lechler, 1998. "Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression," Nature, Nature, vol. 394(6696), pages 897-901, August.
  • Handle: RePEc:nat:nature:v:394:y:1998:i:6696:d:10.1038_29795
    DOI: 10.1038/29795
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    Cited by:

    1. Ming-Ling Chang & Chia-Jung Kuo & Hsin-Chih Huang & Yin-Yi Chu & Cheng-Tang Chiu, 2016. "Association between Leptin and Complement in Hepatitis C Patients with Viral Clearance: Homeostasis of Metabolism and Immunity," PLOS ONE, Public Library of Science, vol. 11(11), pages 1-12, November.
    2. Han Yang & Wenzhi Guo & Jie Li & Shengli Cao & Jiakai Zhang & Jie Pan & Zhihui Wang & Peihao Wen & Xiaoyi Shi & Shuijun Zhang, 2017. "Leptin concentration and risk of coronary heart disease and stroke: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 12(3), pages 1-12, March.
    3. Marko Sysi-Aho & Andrey Ermolov & Peddinti V Gopalacharyulu & Abhishek Tripathi & Tuulikki Seppänen-Laakso & Johanna Maukonen & Ismo Mattila & Suvi T Ruohonen & Laura Vähätalo & Laxman Yetukuri & Tain, 2011. "Metabolic Regulation in Progression to Autoimmune Diabetes," PLOS Computational Biology, Public Library of Science, vol. 7(10), pages 1-16, October.
    4. David Bradley & Alan J. Smith & Alecia Blaszczak & Dharti Shantaram & Stephen M. Bergin & Anahita Jalilvand & Valerie Wright & Kathleen L. Wyne & Revati S. Dewal & Lisa A. Baer & Katherine R. Wright &, 2022. "Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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