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 Ma, Danika 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 () and Di Yu ()
Additional contact information
Jun Deng: Shanghai Jiao Tong University School of Medicine
Qian Chen: The University of Hong Kong
Zhian Chen: Australian National University
Kaili Liang: Shanghai Jiao Tong University School of Medicine
Xin Gao: Shanghai Jiao Tong University School of Medicine
Xiaohui Wang: The University of Hong Kong
Fadzai V. Makota: Australian National University
Hong Sheng Ong: Australian National University
Yanmin Wan: 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
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
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
Liwei Lu: The University of Hong Kong
Di Yu: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23220-x

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