The Role of T Cells in Atopic Dermatitis Pathogenesis

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Atopic dermatitis exemplifies a chronic inflammatory disease primarily driven by adaptive immune dysfunction within T-cell subsets, with T cells influencing multiple disease elements including barrier disruption, immune dysregulation, neuronal hypersensitivity, and microbial dysbiosis. The production of cytokines across various T-cell subsets drives these interconnected pathological processes. While traditionally viewed as a type 2 T helper cell–driven disease, emerging evidence suggests broader T-cell subset involvement, requiring expanded therapeutic targeting beyond the classic IL-4, IL-13, and IL-5 pathway.

The disease ontogeny involves complex antigen presentation processes where barrier disruption allows allergens and antigens to penetrate skin, leading to dendritic cell activation and subsequent naive T-cell priming. Dr Eichenfield describes how various antigen-presenting cells, including Langerhans cells, macrophages, and B cells, influence T-cell differentiation in Th1, Th2, Th17, Th22, and memory T-cell populations. This activation cascade involves multiple cell types, including fibroblasts and epithelial cells that mediate ongoing inflammatory responses with potential for amplification during flares or de-amplification during disease control.

The recognition of broader T-cell involvement beyond type 2 helper cells opens new therapeutic avenues targeting earlier stages of immune activation. While direct therapeutics against individual cytokines such as IL-17, interferon-gamma, and IL-22 have not fully revealed their roles, the evidence suggests multipathway T-cell involvement requiring more comprehensive therapeutic approaches. This understanding drives interest in costimulatory molecule targeting, such as OX40-OX40L interactions, which could potentially address the upstream T-cell activation processes that govern multiple downstream inflammatory pathways simultaneously.