T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.

Abstract

T cell immunosenescence refers to the progressive functional decline of T lymphocytes with aging, characterized by the phenotypic markers, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP), representing a pivotal aspect of overall immune aging. This review systematically elucidates the critical role of T cell immunosenescence in the pathogenesis of common inflammatory skin diseases, including psoriasis, atopic dermatitis, rosacea, and seborrheic dermatitis. Senescent T cells drive the production of a disease-specific SASP via internally dysregulated signaling networks such as NF-κB, JAK-STAT, p38 MAPK, and PI3K-Akt-mTOR pathways, thereby shaping and sustaining a chronic cutaneous inflammatory microenvironment that promotes disease chronicity and recurrence. Furthermore, this review summarizes current therapeutic strategies targeting these senescence-associated pathways and SASP components, discussing both biological agents and small molecule inhibitors. Finally, we propose future research directions focusing on the direct targeting of senescent T cells or their upstream regulatory hubs to achieve deep disease remission and overcome therapeutic resistance.