{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:10:38Z","timestamp":1787613038648,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Miami Dr. Phillip Frost Department of Dermatology &amp; Cutaneous Surgery"},{"name":"University of Miami Miller School of Medicine Dean\u2019s Research Excellence"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interleukin (IL)-15 is primarily known as a pro-inflammatory and anti-apoptotic cytokine, which stimulates the proliferation and survival of key immunocytes, including macrophages (MACs). Yet, it remains unclear how IL-15 specifically impacts MACs in intact human skin, particularly immunoinhibitory, IL-10-producing\/secreting M2 MACs (CD206+IL-10+). In the current pilot study, we explored this in organ-cultured healthy human eyelid skin in the presence of IFN\u03b3 (100 IU\/mL) to mimic a pro-inflammatory signaling milieu found in several chronic immunodermatoses. Quantitative immunohistomorphometry showed that IFN\u03b3 significantly reduced the number of CD68+MACs, M2 CD206+MACs, and immunoinhibitory CD206+IL-10+MACs. Moreover, co-administering recombinant human (rh) IL-15 after inducing inflammation by IFN\u03b3 largely reversed the IFN\u03b3-induced decline in MAC populations. To investigate if this was mediated via the private IL-15 receptor alpha (IL-15R\u03b1), we successfully silenced IL-15R\u03b1 in human skin ex vivo. Indeed, co-administration of IL-15R\u03b1 siRNA abrogated the rhIL-15 protection of M2 CD206+MACs against IFN\u03b3, but not of the CD206+IL-10+MAC subpopulation. These pilot data suggest that IL-15 maintains immunoinhibitory M2 CD206+IL-10+MACs in human skin under IFN\u03b3-dominated inflammatory conditions. Therefore, it deserves to be explored whether IL-15 or IL-15R\u03b1 agonists can exert therapeutic benefit in chronic inflammatory dermatoses by preserving the intracutaneous pool of anti-inflammatory dermal M2 MACs.<\/jats:p>","DOI":"10.3390\/ijms26167811","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T15:53:27Z","timestamp":1755100407000},"page":"7811","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["IL-15 Promotes the Survival of Anti-Inflammatory (M2), Immunoinhibitory (IL-10+) Dermal Macrophages in Human Eyelid Skin Under IFN\u03b3-Dominated Inflammatory Conditions"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1770-308X","authenticated-orcid":false,"given":"Dana-Lee","family":"Demetrius","sequence":"first","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7272-206X","authenticated-orcid":false,"given":"Sofia M.","family":"Perez","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6012-0229","authenticated-orcid":false,"given":"Takahiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"},{"name":"Department of Dermatology, Hamamatsu University, Hamamatsu 431-3192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gherardini","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"},{"name":"CUTANEON\u2013Skin & Hair Innovations GmbH, 22335 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Lee","sequence":"additional","affiliation":[{"name":"Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33125, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9my","family":"Ch\u00e9ret","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"},{"name":"CUTANEON\u2013Skin & Hair Innovations GmbH, 22335 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Paus","sequence":"additional","affiliation":[{"name":"Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 33125, USA"},{"name":"CUTANEON\u2013Skin & Hair Innovations GmbH, 22335 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"He, X., Gao, X., and Xie, W. 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