{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:03:56Z","timestamp":1784178236121,"version":"3.55.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"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. Immunol."],"abstract":"<jats:p>\n                    The concept of tissue-resident memory T (T\n                    <jats:sub>RM<\/jats:sub>\n                    ) cells has fundamentally transformed our understanding of peripheral immune surveillance. Although skin T\n                    <jats:sub>RM<\/jats:sub>\n                    biology has been extensively studied, most investigations have focused on the dermis, whereas the epidermis has traditionally been regarded primarily as a physical barrier composed predominantly of keratinocytes. However, accumulating evidence has demonstrated that the normal human epidermis harbors abundant populations of resident T cells, including both conventional and regulatory T\n                    <jats:sub>RM<\/jats:sub>\n                    cells, indicating that the epidermis is a highly specialized immunological compartment. In this review, we summarize current knowledge regarding the origin, composition, phenotype, and dynamics of human epidermal T\n                    <jats:sub>RM<\/jats:sub>\n                    cells, with particular emphasis on studies performed in human tissues. Epidermal T\n                    <jats:sub>RM<\/jats:sub>\n                    cells are enriched for CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD69\n                    <jats:sup>+<\/jats:sup>\n                    CD103\n                    <jats:sup>+<\/jats:sup>\n                    populations and include specialized cytotoxic subsets expressing CD49a and CD101, whereas regulatory T\n                    <jats:sub>RM<\/jats:sub>\n                    cells constitute a distinct epithelial regulatory network that contributes to local immune tolerance. We also discuss recent advances demonstrating that epidermal T\n                    <jats:sub>RM<\/jats:sub>\n                    cells actively patrol the epidermis, interact closely with Langerhans cells, and participate in the maintenance of epidermal immune homeostasis. Furthermore, emerging evidence implicates epidermal T\n                    <jats:sub>RM<\/jats:sub>\n                    cells in a variety of human diseases, including HIV infection, fixed drug eruption, vitiligo, and alopecia areata. Collectively, these findings support a model in which conventional T\n                    <jats:sub>RM<\/jats:sub>\n                    cells, regulatory T\n                    <jats:sub>RM<\/jats:sub>\n                    cells, Langerhans cells, and keratinocytes form an integrated epidermal immune ecosystem that balances immune surveillance and immune regulation. Recognition of this cellular network challenges the traditional dermis-centric view of cutaneous immunity and suggests that the epidermis should be regarded as an autonomous immunological compartment. A deeper understanding of epidermal immune organization may provide new insights into the pathogenesis and treatment of epidermis-centered diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1903376","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:21:28Z","timestamp":1784175688000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Human epidermal resident memory T cells: beyond the dermal perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Youichi","family":"Ogawa","sequence":"first","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Yamanashi","place":["Yamanashi, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Yamanashi","place":["Yamanashi, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Minai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Yamanashi","place":["Yamanashi, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manao","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Yamanashi","place":["Yamanashi, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Yamanashi","place":["Yamanashi, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuyoshi","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Faculty of Medicine, University of Yamanashi","place":["Yamanashi, 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