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The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses

Author

Listed:
  • Jun Deng

    (Shanghai Jiao Tong University School of Medicine
    The University of Hong Kong
    Shanghai Jiao Tong University School of Medicine)

  • Qian Chen

    (The University of Hong Kong
    Shanghai Jiao Tong University School of Medicine)

  • Zhian Chen

    (Australian National University
    The University of Queensland)

  • Kaili Liang

    (Shanghai Jiao Tong University School of Medicine)

  • Xin Gao

    (Shanghai Jiao Tong University School of Medicine
    Australian National University)

  • Xiaohui Wang

    (The University of Hong Kong)

  • Fadzai V. Makota

    (Australian National University)

  • Hong Sheng Ong

    (Australian National University)

  • Yanmin Wan

    (Fudan University
    Fudan University)

  • Kaiming Luo

    (Shanghai Jiao Tong University School of Medicine)

  • Dongcheng Gong

    (Shanghai Jiao Tong University School of Medicine)

  • Xiang Yu

    (Shanghai Jiao Tong University School of Medicine)

  • Sarina Camuglia

    (Seqirus)

  • Qunxiong Zeng

    (Shanghai Jiao Tong University School of Medicine)

  • Tao Zhou

    (Shanghai Jiao Tong University School of Medicine)

  • Feng Xue

    (Shanghai Jiao Tong University School of Medicine)

  • Jing He

    (Peking University People’s Hospital)

  • Yunbo Wei

    (Qilu University of Technology (Shandong Academy of Sciences))

  • Fan Xiao

    (The University of Hong Kong)

  • Jianyang Ma

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Danika L. Hill

    (Babraham Institute)

  • Wim Pierson

    (Babraham Institute)

  • Thi H. O. Nguyen

    (University of Melbourne, Peter Doherty Institute for Infection and Immunity)

  • Haibo Zhou

    (Shanghai Jiao Tong University School of Medicine)

  • Yan Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Wei Shen

    (Shanghai Jiao Tong University School of Medicine)

  • Lingyun Sun

    (The Affiliated Drum Tower Hospital of Nanjing University Medical School)

  • Zhanguo Li

    (Peking University People’s Hospital)

  • Qiang Xia

    (Shanghai Jiao Tong University School of Medicine)

  • Kun Qian

    (Shanghai Jiao Tong University)

  • Lilin Ye

    (Third Military Medical University
    Chongqing International Institute for Immunology)

  • Steven Rockman

    (Seqirus)

  • Michelle A. Linterman

    (Babraham Institute)

  • Katherine Kedzierska

    (University of Melbourne, Peter Doherty Institute for Infection and Immunity)

  • Nan Shen

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University School of Medicine)

  • Liwei Lu

    (The University of Hong Kong
    Chongqing International Institute for Immunology)

  • Di Yu

    (Shanghai Jiao Tong University School of Medicine
    Australian National University
    The University of Queensland
    Qilu University of Technology (Shandong Academy of Sciences))

Abstract

Follicular helper T (TFH) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate TFH function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying TFH regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations. Leptin promotes mouse and human TFH differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs TFH generation and antibody responses in immunisation and infection. Similarly, leptin deficiency induced by fasting reduces influenza vaccination-mediated protection for the subsequent infection challenge, which is mostly rescued by leptin replacement. Our results identify leptin as a regulator of TFH cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.

Suggested Citation

  • Jun Deng & Qian Chen & Zhian Chen & Kaili Liang & Xin Gao & Xiaohui Wang & Fadzai V. Makota & Hong Sheng Ong & Yanmin Wan & Kaiming Luo & Dongcheng Gong & Xiang Yu & Sarina Camuglia & Qunxiong Zeng & , 2021. "The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23220-x
    DOI: 10.1038/s41467-021-23220-x
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