The Dynamic Role of FOXP3+ Tregs and Their Potential Therapeutic Applications During SARS-CoV-2 Infection

Zhan Xu; Xue Jiang; Xueyu Dai; Bin Li

doi:10.3389/fimmu.2022.916411

The Dynamic Role of FOXP3⁺ Tregs and Their Potential Therapeutic Applications During SARS-CoV-2 Infection

Front Immunol. 2022 Jul 8:13:916411. doi: 10.3389/fimmu.2022.916411. eCollection 2022.

Authors

Zhan Xu¹, Xue Jiang¹, Xueyu Dai¹, Bin Li^{1

2

3

4}

Affiliations

¹ Center for Immune-Related Diseases at Shanghai Institute of Immunology, Department of Respiratory and Critical Care Medicine of Ruijin Hospital, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Thoracic Surgery, Clinical Translational Research Center, Shanghai Pulmonary Hospital, Department of Integrated TCM and Western Medicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
³ Institute of Arthritis Research, Guanghua Integrative Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ Shenzhen Key Laboratory of Immunity and Inflammatory Diseases, Shenzhen, China.

Abstract

Coronavirus disease 2019 (COVID-19) has been raging all around the world since the beginning of 2020, and leads to acute respiratory distress syndrome (ARDS) with strong cytokine storm which contributes to widespread tissue damage and even death in severe patients. Over-activated immune response becomes one of the characteristics of severe COVID-19 patients. Regulatory T cells (Treg) play an essential role in maintaining the immune homeostasis, which restrain excessive inflammation response. So FOXP3⁺ Tregs might participate in the suppression of inflammation caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Besides suppressive function, tissue resident Tregs are also responsible for tissue repair. In this review, we mainly summarize the latest research focusing on the change of FOXP3⁺ Tregs in the COVID-19 patients, discuss the relationship between disease severity and number change of Tregs and speculate the potential role of FOXP3⁺ Tregs during SARS-CoV-2 infection. Furthermore, we introduce some potential Treg-based therapies to improve patients' outcomes, which include small molecular drugs, antibody drugs, CAR-Treg and cytokine treatment. We hope to reduce tissue damage of severe COVID-19 patients and offer better prognosis through Treg-based therapy.

Keywords: COVID-19; FOXP3; SARS-CoV-2; Treg; Treg-based therapy.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / immunology
Cytokine Release Syndrome
Forkhead Transcription Factors
Humans
Inflammation
SARS-CoV-2
T-Lymphocytes, Regulatory* / immunology

Substances

FOXP3 protein, human
Forkhead Transcription Factors