{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:10:08Z","timestamp":1790485808701,"version":"4.1.0"},"reference-count":96,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12302012"],"award-info":[{"award-number":["12302012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, which is mainly caused by the imbalance of immune cells. Current treatment regimens predominately rely on corticosteroids and immunosuppressive agents, accompanied by various side effects. Interleukin-2 (IL-2) is deemed an important cytokine for innate immune cells and adaptive immune cells, especially for the promotion of Treg cells. By combining IL-2\/IL-2R system with engineered T cell-based immunotherapies to enhance the therapeutic efficacy of engineered T cells shows its potential in autoimmune diseases. But the pleiotropy of IL-2 may cause simultaneous stimulation and systemic toxicity, limiting its therapeutic use. There is a growing focus on using IL-2 in combination strategies for synergistic immune enhancement. In this article, we review the IL-2\/IL-2R signaling, including IL-2 dependent signaling and IL-2 independent signaling, and discuss its functions in regulation of different immune cells. In addition, we summarize major clinical application of low-dose IL-2 treatment in SLE with or without other agents, such as rapamycin, tocilizumab and rituximab, present the IL-2 variants and fusion proteins designed for SLE, and highlight the future trends for research on these cytokine-based immunotherapies. It will help to design further optimized IL-2-based therapy for SLE.<\/jats:p>","DOI":"10.3389\/fmed.2025.1552473","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T05:22:39Z","timestamp":1745385759000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A glimpse into the application of the immunomodulatory effect of IL-2 in systemic lupus erythematosus"],"prefix":"10.3389","volume":"12","author":[{"given":"Xin","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1056\/NEJM198512053132327","article-title":"Observations on the systemic administration of autologous 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