Peripheral Blood Skin-Homing T Cells Define Immunological Endotypes in Atopic Dermatitis: A Case-Control Study in a...

Atopic dermatitis (AD) is a chronic inflammatory skin disease with marked immunological heterogeneity. T-cell subsets expressing CLA, CCR4, and CCR10 are involved in skin inflammation, but their frequency and expression patterns in AD remain poorly characterized. This study aimed to define distinct immunological endotypes of AD in the Mexican population by analyzing the frequency of CLA⁺ T cells expressing CCR4 and CCR10, along with their cytokine production profiles.

Flow cytometry quantified CD4⁺ and CD8⁺ T cells in 47 Mexican AD patients, 15 healthy controls, and 16 allergic individuals. Principal component analysis and unsupervised clustering were used to identify immunological patterns.

Two AD endotypes were identified. Endotype 1 exhibited a higher frequency of CD4⁺CLA⁺ T cells (32.1% vs. 21.0%; p = 0.025) and a Th2/Th17-skewed profile, while Endotype 2 showed higher CD8⁺CLA⁺ T-cell frequencies (2.8% vs. 5.5%; p = 0.003) and increased chemokine receptor expression on CD4⁺ T cells (all p < 0.001). Clinically, Endotype 1 presented more active disease at examination (78.9% vs. 35.7%; p < 0.001). Total serum IgE was higher in Endotype 2 (5974 vs. 866 IU/mL; p = 0.032), and both endotypes showed higher IgE than healthy controls. SCORAD, POEM, and DLQI did not clearly separate the endotypes.

AD presents distinct immunological endotypes characterized by specific T-cell profiles, which may inform personalized treatment strategies. This study provides insights into the immunological heterogeneity of AD in the Mexican population and underscores the need for population-specific approaches in disease characterization and management.