Role of signaling lymphocytic activation molecule family of receptors in the pathogenesis of rheumatoid arthritis: insights and application

Yixin Zheng; Jianan Zhao; Mi Zhou; Kai Wei; Ping Jiang; Lingxia Xu; Cen Chang; Yu Shan; Linshuai Xu; Yiming Shi; Steven J Schrodi; Shicheng Guo; Dongyi He

doi:10.3389/fphar.2023.1306584

Role of signaling lymphocytic activation molecule family of receptors in the pathogenesis of rheumatoid arthritis: insights and application

Front Pharmacol. 2023 Nov 6:14:1306584. doi: 10.3389/fphar.2023.1306584. eCollection 2023.

Authors

Yixin Zheng^{1

2

3}, Jianan Zhao^{1

2

3}, Mi Zhou^{1

3}, Kai Wei^{1

2

3}, Ping Jiang^{1

2

3}, Lingxia Xu⁴, Cen Chang^{1

2

3}, Yu Shan^{1

2

3}, Linshuai Xu^{1

2

3}, Yiming Shi^{1

2

3}, Steven J Schrodi^{5

6}, Shicheng Guo^{5

6}, Dongyi He^{1

2

3

7}

Affiliations

¹ Department of Rheumatology, Shanghai Guanghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Guanghua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Institute of Arthritis Research in Integrative Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, China.
⁴ Department of Rheumatology, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, China.
⁵ Center for Human Genomics and Precision Medicine, University of Wisconsin-Madison, Madison, WI, United States.
⁶ Department of Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States.
⁷ Arthritis Institute of Integrated Traditional and Western Medicine, Shanghai Chinese Medicine Research Institute, Shanghai, China.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and joint damage. The signaling lymphocytic activation molecule (SLAMF) family of receptors are expressed on various hematopoietic and non-hematopoietic cells and can regulate both immune cell activation and cytokine production. Altered expression of certain SLAMF receptors contributes to aberrant immune responses in RA. In RA, SLAMF1 is upregulated on T cells and may promote inflammation by participating in immune cell-mediated responses. SLAMF2 and SLAMF4 are involved in regulating monocyte tumor necrosis factor production and promoting inflammation. SLAMF7 activates multiple inflammatory pathways in macrophages to drive inflammatory gene expression. SLAMF8 inhibition can reduce inflammation in RA by blocking ERK/MMPs signaling. Of note, there are differences in SLAMF receptor (SFR) expression between normal and arthritic joint tissues, suggesting a role as potential diagnostic biomarkers. This review summarizes recent advances on the roles of SLAMF receptors 1, 2, 4, 7, and 8 in RA pathogenesis. However, further research is needed to elucidate the mechanisms of SLAMF regulation of immune cells in RA. Understanding interactions between SLAMF receptors and immune cells will help identify selective strategies for targeting SLAMF signaling without compromising normal immunity. Overall, the SLAMF gene family holds promise as a target for precision medicine in RA, but additional investigation of the underlying immunological mechanisms is needed. Targeting SLAMF receptors presents opportunities for new diagnostic and therapeutic approaches to dampen damaging immune-mediated inflammation in RA.

Keywords: biomarker; immunity; inflammation; rheumatoid arthritis; the signaling lymphocytic activation molecule family of receptors.

Publication types

Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the National Natural Science Funds of China (82074234 and 82071756), Shanghai Chinese Medicine Development Office, National Administration of Traditional Chinese Medicine, Regional Chinese Medicine (Specialist) Diagnosis and Treatment Center Construction Project-Rheumatology, State Administration of Traditional Chinese Medicine, National TCM Evidence-Based Medicine Research and Construction Project, Basic TCM Evidence-Based Capacity Development Program, Shanghai Municipal Health Commission, East China Region-based Chinese and Western Medicine Joint Disease Specialist Alliance, Shanghai He Dongyi Famous Chinese Medicine Studio Construction Project (SHGZS-202220), and Shanghai 13th Five-Year Key Specialized College—Department of Osteoarthritis and Arthritis of Integrated Traditional Chinese and Western Medicine (shslczdzk04801).