Mechanisms of exTreg induction

Vikas Saxena; Ram Lakhan; Jegan Iyyathurai; Jonathan S Bromberg

doi:10.1002/eji.202049123

Mechanisms of exTreg induction

Eur J Immunol. 2021 Aug;51(8):1956-1967. doi: 10.1002/eji.202049123. Epub 2021 May 27.

Authors

Vikas Saxena^{1

2}, Ram Lakhan^{1

2}, Jegan Iyyathurai^{1

2}, Jonathan S Bromberg^{1

2

3}

Affiliations

¹ Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
² Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA.
³ Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

CD4⁺ CD25⁺ Foxp3⁺ Tregs play an important role in the maintenance of the immune system by regulating immune responses and resolving inflammation. Tregs exert their function by suppressing other immune cells and mediating peripheral self-tolerance. Under homeostatic conditions, Tregs are stable T-cell populations. However, under inflammatory environments, Tregs are converted to CD4⁺ CD25^low Foxp3^low cells. These cells are termed "exTreg" or "exFoxp3" cells. The molecular mechanism of Treg transition to exTregs remains incompletely understood. Uncertainties might be explained by a lack of consensus of biological markers to define Treg subsets in general and exTregs in particular. In this review, we summarize known markers of Tregs and factors responsible for exTreg generation including cytokines, signaling pathways, transcription factors, and epigenetic mechanisms. We also identify studies demonstrating the presence of exTregs in various diseases and sources of exTregs. Understanding the biology of Treg transition to exTregs will help in designing Treg-based therapeutic approaches.

Keywords: Regulatory T cells ⋅ exTregs ⋅ exFoxp3 ⋅ Treg plasticity ⋅ Treg stability.

Mechanisms of exTreg induction

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