The Role of Tissue Resident Memory Cells in Immunodermatological Disorders

Tissue-resident memory T cells (TRMs) are a distinct memory T-cell subset that permanently reside in tissues such as the skin. In chronic immune-mediated dermatoses, including psoriasis, atopic dermatitis, and vitiligo, TRMs are implicated in site-specific "disease memory," contributing to persistence and relapse at previously affected sites. This review synthesizes emerging concepts on TRMs in chronic inflammatory skin diseases and discusses clinical and translational implications, including TRM-targeted therapies. Original human, animal, or in vitro studies evaluating TRMs in the pathogenesis or persistence of dermatologic diseases were included. In psoriasis, CD8⁺ TRMs (CD69⁺CD103⁺) persisted in clinically healed skin. For atopic dermatitis, both CD4⁺ and CD8⁺ TRMs are implicated in maintaining Th2/Th22 inflammation. In vitiligo, autoreactive CD8⁺ TRMs at lesional margins mediate melanocyte destruction. Across dermatological diseases, TRMs share three core features: persistence in previously affected skin after clinical resolution, rapid reactivation by diverse triggers (stress, autoantigens, allergens, or cytokines) leading to site-specific recurrence, and relative resistance to conventional therapies. Together, these properties provide a unifying framework linking tissue immune memory to the chronic, relapsing nature of inflammatory skin diseases. However, the dominant TRM pathways vary by disease, reflecting differences in immune polarization and antigen specificity. Targeting TRMs represents a promising strategy for disease control and serves as a biomarker of residual disease or flare.