Resident memory T cells in nonlesional skin and healed lesions of patients with chronic inflammatory diseases: Appearances can be deceptive

Tissue -resident memory T (TRM) cells serve as a first line of defense in peripheral tissues to protect the organism against foreign pathogens. However, autoreactive TRM cells are increasingly implicated in autoimmunity, as evidenced in chronic autoimmune and inflammatory skin conditions. This highlights the need to characterize their phenotype and understand their role for the purpose of targeting them specifically without affecting local immunity. To date, the investigation of TRM cells in human skin diseases has focused mainly on lesional tissues of patients. Accumulating evidence suggests that self -reactive TRM cells are still present in clinically healed lesions of patients and play a role in disease flares, but TRM cells also populate skin that is apparently normal. This review discusses the ontogeny of TRM cells in the skin as well as recent insights regarding the presence of self -reactive TRM cells in both clinically healed skin and nonlesional skin of patients with autoimmune and inflammatory skin conditions, with a particular focus on psoriasis, atopic dermatitis, and vitiligo. (J Allergy Clin Immunol 2024;153:606-14.)