The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses
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Published:2021-05-24
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Deng JunORCID, Chen Qian, Chen Zhian, Liang Kaili, Gao Xin, Wang Xiaohui, Makota Fadzai V., Ong Hong Sheng, Wan Yanmin, Luo KaimingORCID, Gong Dongcheng, Yu Xiang, Camuglia Sarina, Zeng Qunxiong, Zhou Tao, Xue Feng, He JingORCID, Wei Yunbo, Xiao Fan, Ma Jianyang, Hill Danika L., Pierson Wim, Nguyen Thi H. O.ORCID, Zhou Haibo, Wang Yan, Shen Wei, Sun Lingyun, Li ZhanguoORCID, Xia Qiang, Qian KunORCID, Ye Lilin, Rockman Steven, Linterman Michelle A.ORCID, Kedzierska KatherineORCID, Shen NanORCID, Lu LiweiORCID, Yu DiORCID
Abstract
AbstractFollicular 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.
Funder
Department of Health | National Health and Medical Research Council
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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