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Treg plasticity and human diseases

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Abstract

Introduction

As a subset of CD4+ T cells, regulatory T cells (Tregs) with the characteristic expression of transcription factor FOXP3 play a key role in maintaining self-tolerance and regulating immune responses. However, in some inflammatory circumstances, Tregs can express cytokines of other T help (Th) cells by internal reprogramming, which is called Treg plasticity. These reprogrammed Tregs with impaired suppressive ability contribute to the progression of diseases by secreting pro-inflammatory cytokines. However, in the tumor microenvironment (TME), such changes in phenotype rarely occur in Tregs, on the contrary, Tregs usually display a stronger suppressive function and inhibit anti-tumor immunity. It is important to understand the mechanisms of Treg plasticity in inflammatory diseases and cancers.

Objectives

In this review, we summarize the characteristics of different Th-like Tregs and discuss the potential mechanisms of these changes in phenotype. Furthermore, we summarize the Treg plasticity in human diseases and discuss the effects of these changes in phenotype on disease progression, as well as the potential application of drugs or reagents that regulate Treg plasticity in human diseases.

Conclusions

Treg plasticity is associated with inflammatory diseases and cancers. Regulating Treg plasticity is a promising direction for the treatment of inflammatory diseases and cancers.

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Data sharing not applicable to this article as no data sets were generated or analyzed during the current study.

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Funding

This study was funded by the National Natural Science Foundation of China, Grant Number 82170966 and 81970933, the International Scientific Collaboration Project of Hubei Province, Grant Number 2022EHB036, and the Fundamental Research Funds for the Central Universities, grant number, 2042023kfyq02.

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  1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China

    Zheng Zhang, Jihua Guo & Rong Jia

  2. Department of Endodontics, School & Hospital of Stomatology, Wuhan University, Wuhan, 430072, China

    Jihua Guo

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  1. Zheng Zhang
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ZZ conceived the review and wrote the manuscript. JHG conceived the review and revised the manuscript. RJ conceived the review and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Rong Jia.

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Zhang, Z., Guo, J. & Jia, R. Treg plasticity and human diseases. Inflamm. Res. 72, 2181–2197 (2023). https://doi.org/10.1007/s00011-023-01808-x

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