Journal article

The metabolic hormone leptin promotes the function of T-FH cells and supports vaccine responses

Jun Deng, Qian Chen, Zhian Chen, Kaili Liang, Xin Gao, Xiaohui Wang, Fadzai 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 Show all

NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021

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 ..

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Grants

Awarded by National Natural Science Foundation of China


Awarded by Australian National Health and Medical Research Council


Awarded by Chongqing International Institute for Immunology, Chongqing


Awarded by Hong Kong Research Grants Council


Awarded by Shandong Provincial Natural Science Foundation of Shandong Province


Awarded by European Research Council Start Grant TWILIGHT


Awarded by Biotechnology and Biological Sciences Research Council


Funding Acknowledgements

We acknowledge the Faculty Core Facility (The University of Hong Kong), and animal facilities (The University of Hong Kong, Australian National University, and Renji Hospital). We thank P. Zhou (Yu lab at Australia National University), S. Cheng (The University of Hong Kong), J. Yao and P. Zhou (Renji Hospital) and M. Biondi and N. Wilson (Seqirus) for technical assistance; and E. Bartlett and C. Vinuesa (The Australian National University) for reading the manuscript. This work was supported by the National Natural Science Foundation of China (31600708, 82071816, 82071792 to J.D., 91842304, 81373195 to L.L.), the Australian National Health and Medical Research Council (GNT1085509 and GNT1147769 to D.Y.), Chongqing International Institute for Immunology, Chongqing (2020YJC10 to L.L), Hong Kong Research Grants Council (HKU 772712M to L.L.), the Special Foundation of Taishan Overseas Distinguished Experts and Scholars, the Priority Research Program of the Shandong Academy of Sciences, Key lab foundation of Shandong Academy of Sciences, the Shandong Provincial Natural Science Foundation of Shandong Province (ZR2020ZD41, ZR2016YL013, ZR2015YL005). The Bellberry-Viertel Senior Medial Research Fellowship (D.Y.), European Research Council Start Grant TWILIGHT (637801 to M.A.L.), Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0407 and BBS/E/B/000C0409 to M.A.L.) and intramural funds from Innovative Research Team of High-Level Local Universities in Shanghai, Renji Hospital, The Australian National University and The University of Queensland (D.Y.).