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Pathogen-associated T follicular helper cell plasticity is critical in anti-viral immunity

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Abstract

T follicular helper (Tfh) cells are critical in providing help for B cells in the germinal center reaction. Tfh cell plasticity, especially with regard to their expression of effector Th cytokines, has been described, but lacks in-depth analysis with genetic approaches. In this study, we systemically compared transcriptomic profiles of Tfh cells derived from various types of immune responses and found gene clusters corresponding to effector Th cells were differentially induced in response to pathogens or immune responses. Of special interest, a subset of Tfh cells producing IFN-γ was generated in an influenza virus infection, partially dependent on the innate cytokine IL-12. Lineage-tracing mouse model revealed unique developmental regulation of IFN-γ+ Tfh cells, while selective ablation of these cells impaired the induction of IgG2c+ germinal center B cells and the control of influenza infection. These results indicate that pathogen-associated Tfh cell plasticity is necessary for host immunity, which has implications in vaccine design.

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (31630022, 31821003, 31991170 and 31600718) and Beijing Municipal Science and Technology (Z181100001318007 and Z171100000417005). We thank Dr. Junling Liu for providing Il12b−/− mice, Dr. Xiaoping Chen for providing the SEA reagent, and the Tsinghua University Institute for Immunology Core facility for FACS sorting.

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Authors and Affiliations

  1. Institute for Immunology, Tsinghua University, Beijing, 100084, China

    Han Feng, Xiaohong Zhao, Xue Bai, Weiwei Fu, Xiaohu Wang & Chen Dong

  2. Discovery Immunology, Bristol Myers Squibb, Princeton, NJ, 08543, USA

    Jenny Xie

  3. Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, China

    Weiwei Fu

  4. CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China

    Hairong Chen & Hong Tang

  5. CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200025, China

    Hong Tang

  6. Pasteurien College, Suzhou University, Suzhou, 215123, China

    Hong Tang

  7. Shanghai Immune Therapy Institute, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, 200127, China

    Chen Dong

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  1. Han Feng
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  2. Xiaohong Zhao
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Feng, H., Zhao, X., Xie, J. et al. Pathogen-associated T follicular helper cell plasticity is critical in anti-viral immunity. Sci. China Life Sci. 65, 1075–1090 (2022). https://doi.org/10.1007/s11427-021-2055-x

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