Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Yi-Giien Tsai; Pei-Fen Liao; Kai-Hung Hsiao; Hung-Ming Wu; Ching-Yuang Lin; Kuender D Yang

doi:10.3389/fimmu.2023.1230264

Pathogenesis and novel therapeutics of regulatory T cell subsets and interleukin-2 therapy in systemic lupus erythematosus

Front Immunol. 2023 Sep 12:14:1230264. doi: 10.3389/fimmu.2023.1230264. eCollection 2023.

Authors

Yi-Giien Tsai^{1

2

3

4}, Pei-Fen Liao^{3

5}, Kai-Hung Hsiao⁶, Hung-Ming Wu⁷, Ching-Yuang Lin⁸, Kuender D Yang^{9

10}

Affiliations

¹ Department of Pediatrics, Changhua Christian Children's Hospital, Changhua, Taiwan.
² School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁴ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
⁵ Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁶ Department of Allergy, Immunology and Rheumatology, Changhua Christian Hospital, Changhua, Taiwan.
⁷ Department of Neurology, Changhua Christian Hospital, Changhua, Taiwan.
⁸ Division of Pediatric Nephrology, Children's Hospital, China Medical University Hospital, Taichung, Taiwan.
⁹ Department of Pediatrics, Mackay Memorial Hospital, New Taipei City, Taiwan.
¹⁰ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Abstract

Systemic lupus erythematosus (SLE) is a heterogeneous multisystem inflammatory disease with wide variability in clinical manifestations. Natural arising CD4+ regulatory T cells (Tregs) play a critical role in maintaining peripheral tolerance by suppressing inflammation and preventing autoimmune responses in SLE. Additionally, CD8+ regulatory T cells, type 1 regulatory T cells (Tr1), and B regulatory cells also have a less well-defined role in the pathogenesis of SLE. Elucidation of the roles of various Treg subsets dedicated to immune homeostasis will provide a novel therapeutic approach that governs immune tolerance for the remission of active lupus. Diminished interleukin (IL)-2 production is associated with a depleted Treg cell population, and its reversibility by IL-2 therapy provides important reasons for the treatment of lupus. This review focuses on the pathogenesis and new therapeutics of human Treg subsets and low-dose IL-2 therapy in clinical benefits with SLE.

Keywords: B regulatory cells; interleukin-2; lupus nephritis; regulatory T cells; systemic lupus erythematosus.

Publication types

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

MeSH terms

CD4-Positive T-Lymphocytes
Humans
Interleukin-2
Lupus Erythematosus, Systemic* / drug therapy
T-Lymphocyte Subsets
T-Lymphocytes, Regulatory*

Substances

Interleukin-2

Grants and funding

This study was supported by the Ministry of Science and Technology (grant number MOST 111-2314-B-371-006, NSTC 112-2314-B-371-006) in Taiwan, Changhua Christian Hospital (112-CCH-IRP-022; 112-CCH-ICO-152; 111-CCH-IRP-018; 110-CCH-IRP-030, 110-CCH-ICO-152), and Academia Sinica, Taiwan (AS-SS-111-02-1).