Zhengjiang Wang,1,2,* Jiaqi Xu,1,2,* Liqun Mo,1 Renshu Zhan,1,2 Jin Zhang,3 Li Liu,1,2 Jun Jiang,4 Yingying Zhang,1,2 Yiping Bai1,2 

1Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 3Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA; 4Department of General Surgery (Thyroid Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yingying Zhang; Yiping Bai, Email yingyingzhang917@gmail.com; baiyiping0608@163.com

Abstract: Irisin is a muscle factor induced by exercise, generated through the proteolytic cleavage of the membrane protein fibronectin type III domain-containing protein 5 (FNDC-5). Numerous studies have shown that irisin plays a significant role in regulating glucose and lipid metabolism, inhibiting oxidative stress, reducing systemic inflammatory responses, and providing neuroprotection. Additionally, irisin can exert immunomodulatory functions by regulating regulatory T cells (Tregs). Tregs are a highly differentiated subset of mature T cells that play a key role in maintaining self-immune homeostasis and are closely related to infections, inflammation, immune-related diseases, and tumors. Irisin exerts persistent positive effects on Treg cell functions through various mechanisms, including regulating Treg cell differentiation and proliferation, improving their function, modulating the balance of immune cells, increasing the production of anti-inflammatory cytokines, and enhancing metabolic functions, thereby helping to maintain immune homeostasis and prevent immune-related diseases. As an important myokine, irisin interacts with receptors on the cell membrane, activating multiple intracellular signaling pathways to regulate cell metabolism, proliferation, and function. Although the specific receptor for irisin has not been fully identified, integrins are considered potential receptors. Irisin activates various signaling pathways, including AMPK, MAPK, and PI3K/Akt, through integrin receptors, thereby exerting multiple biological effects. These research findings provide important clues for understanding the mechanisms of irisin’s action and theoretical basis for its potential applications in metabolic diseases and immunomodulation. This article reviews the relationship between irisin and Tregs, as well as the research progress of irisin in immune-related diseases such as multiple sclerosis, myasthenia gravis, acquired immune deficiency syndrome, type 1 diabetes, sepsis, and rheumatoid arthritis. Studies have revealed that irisin plays an important role in immune regulation by improving the function of Tregs, suggesting its potential application value in the treatment of immune-related diseases.

Keywords: irisin, FNDC5, regulatory T cell, immunity, immune-related diseases