{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:25:30Z","timestamp":1792113930946,"version":"4.4.0"},"reference-count":162,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"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>Tissue resident memory T (T<jats:sub>RM<\/jats:sub>) cells reside in peripheral, non-lymphoid tissues such as the skin, where they act as alarm-sensor cells or cytotoxic cells.\u00a0Physiologically, skin T<jats:sub>RM<\/jats:sub>cells persist for a long term and can be reactivated upon reinfection with the same antigen,\u00a0thus serving as peripheral sentinels in the immune surveillance network. CD8<jats:sup>+<\/jats:sup>CD69<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>\u00a0T<jats:sub>RM<\/jats:sub>\u00a0cells are the well-characterized subtype that develops in the\u00a0epidermis. The local mediators such as interleukin (IL)-15 and transforming growth factor (TGF)-\u03b2 are required for the formation of long-lived T<jats:sub>RM<\/jats:sub>cell population in skin. Skin\u00a0T<jats:sub>RM<\/jats:sub>\u00a0cells engage virus-infected cells, proliferate<jats:italic>in situ<\/jats:italic>in response to local antigens and do not migrate out of the epidermis. Secondary T<jats:sub>RM<\/jats:sub>\u00a0cell populations are derived from pre-existing T<jats:sub>RM<\/jats:sub>\u00a0cells and newly recruited T<jats:sub>RM<\/jats:sub>precursors from the circulation. In addition to microbial pathogens, topical application of chemical allergen to skin causes delayed-type hypersensitivity and amplifies the number of antigen-specific CD8<jats:sup>+<\/jats:sup>\u00a0T<jats:sub>RM<\/jats:sub>\u00a0cells at challenged site. Skin T<jats:sub>RM<\/jats:sub>cells are also involved in the pathological conditions, including vitiligo, psoriasis, fixed drug eruption and cutaneous T-cell lymphoma (CTCL). The functions of these T<jats:sub>RM<\/jats:sub>cells seem to be different, depending on each pathology. Psoriasis plaques are seen in a recurrent manner especially at the originally affected sites. Upon stimulation of the skin of psoriasis patients, the CD8<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>CD49a<jats:sup>-<\/jats:sup>T<jats:sub>RM<\/jats:sub>cells in the epidermis seem to be reactivated and initiate IL-17A production. Meanwhile, autoreactive CD8<jats:sup>+<\/jats:sup>CD103<jats:sup>+<\/jats:sup>CD49a<jats:sup>+<\/jats:sup>T<jats:sub>RM<\/jats:sub>\u00a0cells secreting interferon-\u03b3 are present in lesional\u00a0vitiligo\u00a0skin. Fixed\u00a0drug eruption\u00a0is another disease where skin T<jats:sub>RM<\/jats:sub>cells evoke its characteristic clinical appearance upon administration of a causative drug. Intraepidermal CD8<jats:sup>+<\/jats:sup>T<jats:sub>RM<\/jats:sub>cells with an effector-memory\u00a0phenotype\u00a0resident\u00a0in\u00a0the skin lesions of fixed\u00a0drug eruption\u00a0play a major contributing role in the development of localized tissue damage. CTCL develops primarily in the skin by a clonal expansion of a transformed T<jats:sub>RM<\/jats:sub>cells.\u00a0CD8<jats:sup>+<\/jats:sup>CTCL with the pagetoid epidermotropic histology is considered to originate from epidermal CD8<jats:sup>+<\/jats:sup>T<jats:sub>RM<\/jats:sub>cells. This review will discuss the current understanding of skin T<jats:sub>RM<\/jats:sub>biology and their contribution to skin homeostasis and diseases.<\/jats:p>","DOI":"10.3389\/fimmu.2020.618897","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T05:46:15Z","timestamp":1612331175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":124,"title":["Pathophysiology of Skin Resident Memory T 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