Tissue-Resident Memory and Follicular/Peripheral Helper PD-1⁺ T Cells Infiltrate Lesional Skin in Atopic Dermatitis

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Atopic dermatitis (AD) is a chronic inflammatory skin disease primarily associated with Th2 cell responses.
• While Th2 pathways are targeted, a comprehensive understanding of both adaptive and innate immune cells in lesional versus nonlesional skin is lacking.
• Existing therapies address some unmet needs, emphasizing the importance of detailed immune profiling.

Purpose of the Study:

• To comprehensively characterize the adaptive and innate immune cell landscape in lesional (L) versus nonlesional (NL) skin of patients with atopic dermatitis.
• To identify specific immune cell populations and their associated cytokine profiles that correlate with disease severity.
• To explore potential novel therapeutic targets by elucidating the immune microenvironment in AD.

Main Methods:

• Paired lesional and nonlesional skin biopsies and matched blood samples were collected from 10 AD patients.
• Multiparameter flow cytometry was employed to analyze the immunophenotype and cytokine profiles of immune cells at the single-cell level.
• Unsupervised analysis was utilized to identify distinct immune cell populations and their characteristics.

Main Results:

• Lesional skin showed a predominant infiltration of CD4+CD103+PD-1+ tissue-resident memory T cells (TRMs), which positively correlated with the Eczema Area and Severity Index (EASI).
• Augmented frequencies of skin-resident CD4+CD103-PD-1+CXCR5+CCR5+/- follicular/peripheral helper T cells (Tfh/Tph) were observed in lesional skin.
• Inflammatory monocytes and monocyte-derived dendritic cells (Mo-DCs) were found to positively correlate with CD4+CD103+PD-1+ TRMs and EASI in lesional skin.

Conclusions:

• The study identified specific populations of T cells, including TRMs and Tfh/Tph cells, and innate immune cells like monocytes and Mo-DCs that are significantly altered in lesional AD skin.
• These findings provide a deeper understanding of the complex immune landscape in atopic dermatitis.
• The identified immune cell profiles and their correlations with disease severity may facilitate the development of novel therapeutic strategies for AD.