CD1a-autoreactive T cell sensing of skin barrier compromise.

Authors

Rosana Ottakandathil Babu, Janina Nahler, Kyla Dooley, Karmella Naidoo, Adrian Kobiela, Soo Weei Ng, John H Ye, Esther Bridges, Devika Agarwal, Alison Simmons, Hashem Koohy, Agne Antanaviciute, Anna Adams, Maria Kiourlappou, Peter Todd, Stephen Taylor, Calixte Monast, Carolyn Cuff, Brian D Marsden, Christopher D Buckley, Sandip K Datta, Thomas Freeman, Calliope Dendrou, Holm Uhlig, Monica W L Leung, Marta Polak, Yi-Ling Chen, Graham Ogg

Published in

The British journal of dermatology. Sep 08, 2026. Epub Sep 08, 2026.

Abstract

T cells are often enriched at barrier tissues, yet little is known of their roles in barrier sensing and relevance to associated disease. CD1a is a Major Histocompatibility Complex class I-like molecule expressed by Langerhans cells, which forms complexes with lipid antigens to facilitate recognition by non-classical CD1a-reactive T cells.
Langerhans cells are altered in lesional atopic dermatitis (AD) skin, but the role of CD1a in disease pathogenesis has not been extensively investigated.
Human skin challenge, single cell and spatial transcriptomic based approaches and functional immunology were used to assess the role of CD1a in AD pathogenesis.
Skin allergen challenge in individuals with AD induced skin CCL17 and CCL22 concentrations that promoted CCR4+ T cell migration. Single cell resolution proteo-transcriptomics from human lesional AD skin tissue identified a dominant CCL17/22 source as a persistent population of activated skin CD1a+ dendritic cells (DCs) previously shown to be transiently enriched in human skin wounds. Single-cell resolution spatial tissue analyses showed that these cells were predominantly located within lesional sub-epidermal microcompartment clusters co-localising with distinct subpopulations of Th2 cells. Activated skin DCs expressed neutral sphingomyelinase, which processed inhibitory long chain sphingomyelin to drive Th2 cell CD1a-autoreactivity.
In summary, the findings are consistent with human CD1a-autoreactive T cells sensing of chronic skin barrier compromise through detection of altered sphingomyelin cycle activity, with implications for the pathogenesis of atopic and related disease.

PMID:
42710064
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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