Circulating ex-Trm CD8 + T cells with skin-homing/chemoattraction phenotype are associated with disease severity in atopic dermatitis

Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by skin-homing memory T cells. Recent evidence suggests that a subset of tissue-resident memory T (Trm) cells can exit tissues and recirculate as ex-Trm cells. Methods Peripheral blood memory T cell subpopulations were analyzed in adults with AD, stratified by disease severity, using multiparametric flow cytometry. CD4 + and CD8 + memory subsets and the skin-homing markers CLA, CCR4, and CCR10 were evaluated. Results Overall CD4 + and CD8 + memory T cell distributions were preserved. AD patients showed expansion of CD4 + central memory T cells expressing CLA, CCR4, and CCR10. Most notably, a circulating population of CD8 + ex-Trm cells co-expressing CLA, CCR4, and CCR10 was increased in moderate-to-severe disease and correlated positively with clinical severity. No comparable expansion was observed for CD4 + ex-Trm cells. Discussion Circulating CD8 + ex-Trm cells with skin-homing properties may contribute to AD progression by reseeding distant skin sites and sustaining inflammation, whereas CD4 + ex-Trm cells may remain preferentially retained within inflamed skin. These findings identify circulating CD8 + ex-Trm cells as potential biomarkers of disease severity and disease dissemination.