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; Di Yu

doi:10.1038/s41467-021-23220-x

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 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 journal › Article › peer-review

31 Citations (Scopus)

Abstract

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

Original language	English
Article number	3073
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-23220-x
Publication status	Published - 1 Dec 2021

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Deng, J., Chen, Q., Chen, Z., Liang, K., Gao, X., Wang, X., Makota, F. V., Ong, H. S., Wan, Y., Luo, K., Gong, D., Yu, X., Camuglia, S., Zeng, Q., Zhou, T., Xue, F., He, J., Wei, Y., Xiao, F., ... Yu, D. (2021). The metabolic hormone leptin promotes the function of T_FH cells and supports vaccine responses. Nature Communications, 12(1), Article 3073. https://doi.org/10.1038/s41467-021-23220-x

@article{a38015284dc540bfa0755718884c2ee2,

title = "The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses",

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.",

author = "Jun Deng and Qian Chen and Zhian Chen and Kaili Liang and Xin Gao and Xiaohui Wang and Makota, {Fadzai V.} and Ong, {Hong Sheng} and Yanmin Wan and Kaiming Luo and Dongcheng Gong and Xiang Yu and Sarina Camuglia and Qunxiong Zeng and Tao Zhou and Feng Xue and Jing He and Yunbo Wei and Fan Xiao and Jianyang Ma and Hill, {Danika L.} and Wim Pierson and Nguyen, {Thi H.O.} and Haibo Zhou and Yan Wang and Wei Shen and Lingyun Sun and Zhanguo Li and Qiang Xia and Kun Qian and Lilin Ye and Steven Rockman and Linterman, {Michelle A.} and Katherine Kedzierska and Nan Shen and Liwei Lu and Di Yu",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-23220-x",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Deng, J, Chen, Q, Chen, Z, Liang, K, Gao, X, Wang, X, Makota, FV, Ong, HS, Wan, Y, Luo, K, Gong, D, Yu, X, Camuglia, S, Zeng, Q, Zhou, T, Xue, F, He, J, Wei, Y, Xiao, F, Ma, J, Hill, DL, Pierson, W, Nguyen, THO, Zhou, H, Wang, Y, Shen, W, Sun, L, Li, Z, Xia, Q, Qian, K, Ye, L, Rockman, S, Linterman, MA, Kedzierska, K, Shen, N, Lu, L & Yu, D 2021, 'The metabolic hormone leptin promotes the function of T_FH cells and supports vaccine responses', Nature Communications, vol. 12, no. 1, 3073. https://doi.org/10.1038/s41467-021-23220-x

TY - JOUR

T1 - The metabolic hormone leptin promotes the function of TFH cells and supports vaccine responses

AU - Deng, Jun

AU - Chen, Qian

AU - Chen, Zhian

AU - Liang, Kaili

AU - Gao, Xin

AU - Wang, Xiaohui

AU - Makota, Fadzai V.

AU - Ong, Hong Sheng

AU - Wan, Yanmin

AU - Luo, Kaiming

AU - Gong, Dongcheng

AU - Yu, Xiang

AU - Camuglia, Sarina

AU - Zeng, Qunxiong

AU - Zhou, Tao

AU - Xue, Feng

AU - He, Jing

AU - Wei, Yunbo

AU - Xiao, Fan

AU - Ma, Jianyang

AU - Hill, Danika L.

AU - Pierson, Wim

AU - Nguyen, Thi H.O.

AU - Zhou, Haibo

AU - Wang, Yan

AU - Shen, Wei

AU - Sun, Lingyun

AU - Li, Zhanguo

AU - Xia, Qiang

AU - Qian, Kun

AU - Ye, Lilin

AU - Rockman, Steven

AU - Linterman, Michelle A.

AU - Kedzierska, Katherine

AU - Shen, Nan

AU - Lu, Liwei

AU - Yu, Di

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85106588847&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-23220-x

DO - 10.1038/s41467-021-23220-x

M3 - Article

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3073

ER -

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

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