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Semaphorin 3 a restores the ability of type 1 regulatory T cells to suppress food allergy

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Abstract

Food allergy (FA) is a common immune disorder that involves dysfunctional immune regulation. More remedies for restoring immune regulation are necessary. Semaphorin 3 A (Sema3a) is a secreted protein of the semaphorin family, which plays a role in immune responses at all stages. The objective of this study is to gain an understanding of how Sema3a can restore the immune regulatory abilities of type 1 regulatory T cells (Tr1 cells). In this study, blood samples were taken from patients with FA. Tr1 cells were purified from blood samples using flow cytometry cell sorting, using LAG3 and CD49b as surface markers. RNA sequencing was employed to examine the characteristics of Tr1 cells. We observed an exaggerated increase in ER stress in peripheral Tr1 cells of FA patients. Enforced expression of spliced X-box protein-1 (XBP1s, one of the key molecules in ER stress) resulted in suppression of interleukin (IL)-10 expression in CD4+ T cells. Eukaryotic initiation factor 2a (eIF2a) mediated the effects of XBP1 on suppressing IL-10 expression in Tr1 cells. The use of Sema3a resulted in a decrease in ER stress, and an increase in IL-10 expression in Tr1 cells of FA patients. Sema3a administration reduced experimental FA by increasing the number of Tr1 cells. In conclusion, IL-10 expression in Tr1 cells is disturbed by ER stress. Sema3a treatment restores the expression of IL-10 and the immunosuppressive capability of Tr1 cells.

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Acknowledgements

Not applicable.

Funding

This study was supported by research grants of the National Natural Science Foundation of China (8197033399, 32090052), Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009) and Shenzhen science, technology and innovation committee (KQTD20170331145453160, SGDX20201103095609027, KCXFZ20201221173208023).

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Author notes

  1. Panpan Gao and Shuo Song contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Nutrition, Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China

    Panpan Gao

  2. Department of Gastroenterology, Fifth Affiliated Hospital, Zhengzhou University, Zhengzhou, China

    Panpan Gao, Yanan Wang & Pengyuan Zheng

  3. Marshall Laboratory of Biomedical Engineering, Shenzhen University, Shenzhen, China

    Shuo Song, Huazhen Liu, Xiangyu Wang, Qing shu & Pingchang Yang

  4. Department of General Medicine Practice, Third Affiliated Hospital of Shenzhen University, Shenzhen, China

    Shuo Song & Huazhen Liu

  5. Institute of Allergy & Immunology, State Key Laboratory of Respiratory Disease Shenzhen University Division, Shenzhen University School of Medicine, Shenzhen, China

    Shuo Song, Huazhen Liu & Pingchang Yang

  6. Department of Gastroenterology, Shenzhen Second People’s Hospital, Shenzhen, China

    Xiangyu Wang & Qing shu

Authors
  1. Panpan Gao
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  2. Shuo Song
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  3. Yanan Wang
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  4. Huazhen Liu
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  5. Xiangyu Wang
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  8. Pengyuan Zheng
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Contributions

Gao P, Song S, Wang Y, Liu H, Wang X and Shu Q performed experiments, analyzed data and reviewed the manuscript. Yang P and Zheng P organized the project and supervised experiments. Yang P designed the project and prepared the manuscript.

Corresponding authors

Correspondence to Pingchang Yang or Pengyuan Zheng.

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The experimental protocols were reviewed and approved by the human ethics committee and animal ethics committee at Zhengzhou University.

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Gao, P., Song, S., Wang, Y. et al. Semaphorin 3 a restores the ability of type 1 regulatory T cells to suppress food allergy. Immunol Res 72, 320–330 (2024). https://doi.org/10.1007/s12026-023-09437-6

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  • DOI: https://doi.org/10.1007/s12026-023-09437-6

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