The metabolic hormone leptin promotes the function of T<sub>FH</sub> cells and supports vaccine responses.

Deng, Jun; Chen, Qian; Chen, Zhian; Liang, Kaili; Gao, Xin; Wang, Xiaohui; Makota, Fadzai V; Ong, Hong Sheng et al. · Nat Commun · 2021

basic_science · Level V

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Abstract

Follicular helper T (T<sub>FH</sub>) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate T<sub>FH</sub> function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying T<sub>FH</sub> 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 T<sub>FH</sub> differentiation and IL-21 production via STAT3 and mTOR pathways. Leptin receptor deficiency impairs T<sub>FH</sub> 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 T<sub>FH</sub> cell differentiation and function and indicate low levels of leptin as a risk factor for vaccine failure.

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