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

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, Tao Zhou, Feng Xue, Jing He, Yunbo Wei, Fan Xiao, Jianyang MaDanika L. Hill, Wim Pierson, Thi H.O. Nguyen, Haibo Zhou, Yan Wang, Wei Shen, Lingyun Sun, Zhanguo Li, Qiang Xia, Kun Qian, Lilin Ye, Steven Rockman, Michelle A. Linterman, Katherine Kedzierska, Nan Shen, Liwei Lu*, Di Yu*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    26 Citations (Scopus)

    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.

    Original languageEnglish
    Article number3073
    JournalNature Communications
    Volume12
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2021

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