Abstract
Atopic dermatitis (AD) is primarily driven by Th2 cells. Although CD3(+) T cells and CD11c(+) cells predominate in lesional (L) over nonlesional (NL) skin, both sites harbor epidermal dysregulation and a type 2 profile relative to healthy skin. Therapeutics focusing on Th2-mediated pathways partially fill an unmet medical need, highlighting the importance of further characterizing the adaptive and innate immune landscape in L versus NL skin. Paired L and NL biopsies and matched blood samples were collected from 10 patients. The immunophenotype and cytokine profile of immune cells were examined at the single-cell level using multiparameter flow cytometry and unsupervised analysis. L compared with NL skin was predominantly infiltrated by CD4(+)CD103(+)PD-1(+) tissue-resident memory T cells (TRMs) that positively correlated with disease severity (EASI). CD4(+) CD103(+)PD-1(+) TRMs coexpressed CD25 and ICOS. Frequencies of skin-resident CD4(+)CD103(-)PD-1(+)CXCR5(+)CCR5(+/-) follicular/peripheral helper T cells (Tfh/Tph) were also augmented in L skin. CCR5(-) Tfh/Tph coexpressed ICOS, OX40, and IFN-γ along with IL-4 or CD120b while CCR5(+) Tfh/Tph coexpressed IL-4Rα. Furthermore, inflammatory monocytes and monocyte-derived dendritic cells (Mo-DCs) positively correlated with CD4(+)CD103(+)PD-1(+) TRMs and EASI in L skin. These findings enhance our knowledge of AD's innate and adaptive immune profile which may facilitate the discovery of novel therapeutic targets.