CXCR6+ CD4+ Tissue-Resident Memory T Cells Orchestrate Relapse in Allergic Dermatitis via CXCL16-Dependent Persistence

ABSTRACT: The persistence of CD4+ tissue-resident memory T (TRM) cells is crucial for relapse in allergic skin conditions; however, the mechanisms underlying their maintenance and pathogenic potential remain poorly defined. Here, we identified CXCR6+ CD4+ TRM cells as a distinct pathogenic subset that rapidly induces relapse through cytokine production in allergic dermatitis. This subset requires CXCL16-dependent interactions with CD301b+ conventional dendritic cell subset 2 (cDC2) for in situ maintenance. Functional blockade of the CXCL16–CXCR6 signaling pathway attenuated local TRM proliferation and reduced antigen-induced relapse in murine models. In human atopic dermatitis (AD), CXCR6+ CD4+ TRM cells co-localized with CD301+ cDC2 in perivascular clusters even after successful anti-IL-13 therapy. These findings highlight CXCR6+ CD4+ TRM cells as a pathogenic reservoir sustaining chronic and recurrent inflammation, and propose the CXCL16–CXCR6 axis as a therapeutic target to prevent relapse in allergic skin diseases, such as AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE299966 | GEO | 2026/10/01

REPOSITORIES: GEO