D1.236 - The role of tissue resident memory cells in immunodermatological disorders: A Systematic Review

Tissue‐resident memory T cells (TRMs) are a subset of memory T cells that stay permanently in tissues such as the skin, rather than circulating in the blood. In chronic immune-mediated dermatological disorders, notably psoriasis, atopic dermatitis, and vitiligo, TRMs are thought to drive site-specific ‘disease memory’ leading to persistent or relapsing lesions at the same locations even after therapy. Their prominent presence in lesional skin and association with recurrence have positioned TRMs as key contributors to disease chronicity and attractive targets for therapeutic intervention. Our objective was to systematically review and synthesize current evidence on the role of TRM cells in chronic inflammatory skin diseases, identify key knowledge gaps, and discuss implications for clinical and translational advances, including potential TRM-targeted therapies.

We conducted a systematic review following PRISMA guidelines. Comprehensive searches of PubMed, Embase, Web of Science, Scopus, and Cochrane Library – supplemented by Google Scholar and clinical trial registries – were performed (inception to May 2025) to identify studies examining TRM cells in dermatological conditions. Inclusion criteria were original research (human, animal, or in vitro) focusing on TRM involvement in skin disease pathogenesis or persistence. After screening and eligibility assessment, data from relevant studies were extracted and qualitatively synthesized. In total, 19 studies on psoriasis, 10 on atopic dermatitis, 7 on vitiligo, 7 on allergic contact dermatitis, and 8 on other conditions such as cutaneous lupus, graft-versus-host disease, and drug reactions were included.

Of 2,196 records identified, 51 studies met the inclusion criteria. Psoriasis was the most studied condition, showing that CD8⁺ TRMs (CD69⁺CD103⁺) persist in clinically healed skin. In atopic dermatitis, both CD4⁺ and CD8⁺ TRMs sustain a Th2/Th22 milieu and recruit innate cells during flares. In vitiligo, autoreactive CD8⁺ TRMs at lesional margins contribute to melanocyte destruction and depigmentation. Allergic contact dermatitis and other disorders, including cutaneous lupus, drug reactions, and Graft versus host disease (GVHD), also implicate TRMs in tissue-specific immune persistence or reactivation. Across conditions, TRMs emerge as long-lived pathogenic reservoirs produce pro-inflammatory cytokines (IL-17A, IL-22), and correlate with lesion relapse and therapy resistance.

TRMs are pivotal in sustaining and relapsing immune-mediated skin diseases by serving as long-lived pathogenic sources in the skin. They are promising therapeutic targets, with strategies such as blocking maintenance signals or disrupting tissue retention showing potential for sustained control, as seen in early psoriasis studies. TRM levels or activity may also serve as biomarkers for residual disease or flare risk. Addressing gaps such as standardizing definitions and studying underexplored subsets like CD4⁺ TRMs, could advance their clinical utility. Modulating TRMs may ultimately enable long-term remission and inform tissue-targeted immunotherapies in chronic dermatoses. Modulating TRMs may ultimately enable long-term remission and shape a paradigm shift toward tissue-targeted immunotherapies in chronic dermatoses.