{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:30:53Z","timestamp":1792614653100,"version":"4.5.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Alopecia areata (AA) is a highly prevalent human autoimmune disease. It is now regarded by most scientists as a defect of immune privilege (IP). The impaired IP in the hair follicles is an essential driver of AA, which is developed by the imbalanced local CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell, NK cell, tissue-resident Treg cells and infiltration of many factors such as IFN-\n                    <jats:italic>\u03b3<\/jats:italic>\n                    and TGF-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    . In the past, IL-2 and IL-15 are generally recognized for their roles in promoting pro-inflammatory immune responses. Moreover, cytokine-based therapeutic strategies utilizing IL-2 or IL-15 have the capacity to expand effector T cell and NK cells, thereby offering a viable alternative immunotherapeutic approach for cancer treatment. In contemporary century, there has been a gradually growing recognition of their critical role in modulating immune tolerance (via Treg cell). Low-dose IL-2 preferentially induces Treg cell, recovering the balance status between Treg cell and effector T cell and representing an original strategy for autoimmune systematic diseases. Recent study found IL-15 was the guardian of IP in hair follicles arousing the attention of IL-15 in maintain immune tolerance. IL-15, as a pleiotropic cytokine, shares many overlapping biological functions with IL-2. Notably, IL-15 will replace IL-2 to play a certain role while the level and function of IL-2 has decreased. Low-dose IL-2 and certain concentration of IL-15 complement each other, maintaining the function of Treg cell, and induce reconstruction in immune tolerance, which may be a new strategy for treating alopecia areata. Therefore, refocusing on the function of IL-15 and its role in AA might provide new insights into the pathogenesis and therapy of AA.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1815855","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:11:56Z","timestamp":1787569916000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["IL-15 in alopecia areata: the immune tolerance mechanistic insights and translational perspectives"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiahua","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Dermatovenereology The second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology The second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Joint Program in Transfusion Medicine, Brigham and Women\u2019s Hospital\/Children\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology The second Hospital of Shanxi Medical University","place":["Taiyuan, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1080\/1744666x.2025.2575365","article-title":"Immune therapies for alopecia areata: evidence and new 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