{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:36:53Z","timestamp":1792791413984,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"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. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of autoimmune diseases. Our previous research demonstrated that AGAP2-AS1 in keratinocytes is involved in the pathogenesis of psoriasis, but its effect on CD4<jats:sup>+<\/jats:sup> T cell differentiation remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exosomes were extracted from HaCaT cells using a reagent kit and verified by TEM (Transmission Electron Microscope), NTA (Nanoparticle Tracking Analysis), and Western Blot. We incubated exosomes with CD4<jats:sup>+<\/jats:sup> T cells and detected the distribution of AGAP2-AS1 by fluorescence microscopy. Flow cytometry and ELISA were used to detect CD4<jats:sup>+<\/jats:sup> T cell differentiation. In addition, the relationship between AGAP2-AS1\/miR-424-5p\/SGK1 and its effect on CD4<jats:sup>+<\/jats:sup> T cell differentiation were confirmed by bioinformatics analysis, dual luciferase reporter gene experiments, quantitative real-time PCR, flow cytometry, and ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that exosomes derived from TNF-\u03b1-treated HaCaTs were able to deliver AGAP2-AS1 to CD4<jats:sup>+<\/jats:sup> T cells, promoting Th1 and Th17 differentiation. In CD4<jats:sup>+<\/jats:sup> T cells, AGAP2-AS1 promotes Th1 and Th17 differentiation via the miR-424-5p\/SGK1 axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Psoriatic HaCaTs deliver AGAP2-AS1 to CD4<jats:sup>+<\/jats:sup> T cells via exosomes, inducing Th1 and Th17 differentiation through the miR-424-5p\/SGK1 axis, thereby promoting the progression of psoriasis. These findings provide novel insights into the pathogenesis of psoriasis and potential therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1521470","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:44:22Z","timestamp":1748583862000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Exosomes containing long non-coding RNA AGAP2-AS1 promote the differentiation of CD4+ T cells through the miR-424-5p\/SGK1 axis in psoriasis"],"prefix":"10.3389","volume":"16","author":[{"given":"Ziqi","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglai","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebiao","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, clinical presentation, and treatment of psoriasis: a review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1007\/s10753-023-01857-8","article-title":"Role of serum\/glucocorticoid-regulated kinase 1 (SGK1) in immune and inflammatory diseases","volume":"46","author":"Bian","year":"2023","journal-title":"Inflammation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"7032","DOI":"10.3892\/mmr.2017.7492","article-title":"A novel non-contact communication between human keratinocytes and T cells: exosomes derived from keratinocytes support superantigen-induced proliferation of resting T cells","volume":"16","author":"Cai","year":"2017","journal-title":"Mol. 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