Tissue-Resident Memory T Cells in Atopic Dermatitis: Pathogenic Roles and Therapeutic Prospects: A Narrative Review

Abstract

Atopic dermatitis (AD), commonly known as eczema, is a chronic inflammatory skin condition characterized by itchiness, dryness, and skin barrier dysfunction driven by genetic and environmental factors. Central to AD pathogenesis are tissue-resident memory T cells (TRMs): protective immune cells that reside in tissues long-term but can malfunction in AD to sustain chronic, damaging inflammation for months or years. Therapeutic advances targeting TRM-mediated pathways include rocatinlimab, an anti-OX40 antibody that inhibits T cell activation and memory formation with 47% to 71% of participants achieving a ≥75% reduction in AD severity, and janus kinase (JAK) inhibitors, with which 70% of participants achieved a ≥75% reduction in AD severity. These findings underscore the promise of TRMtargeted therapies for AD management, but there remains an unmet need for safe, effective therapeutics that offer cell-type-specific targeting towards AD’s immunological roots. To that end, adoptive cell therapy (ACT) offers two promising approaches — general autologous ACT and allogeneic induced pluripotent stem cell (iPSC)-based ACT — underexplored therapies for AD that could enable direct TRM targeting. ACT has not been tested in any clinical or preclinical study of AD, nor do existing studies treating other inflammatory conditions establish its efficacy and safety in AD. However, its anti-inflammatory potential in colitis, implant, and arthritis studies highlights the critical need for continued research developing more targeted and effective AD treatments. This article examines the role of TRMs in AD pathogenesis, evaluates emerging T cell treatment strategies, and proposes novel TRM therapeutic applications to help address the various cases of this debilitating condition.