ROLE OF T-CELL SUBTYPES IN PSORIATIC ARTHRITIS SKIN MANIFESTATIONS

Abstract

Psoriatic arthritis (PsA) is a chronic inflammatory disease marked by both joint involvement and characteristic skin manifestations, with T-cell-mediated immune dysregulation playing a central role in its pathogenesis. This study aimed to delineate the immunopathological landscape of psoriatic skin lesions by characterizing the distribution, phenotype, and function of key T-cell subtypes. Skin biopsy samples from PsA patients and healthy controls were analyzed through immunohistochemistry, flow cytometry, multiplex cytokine assays, and qRT-PCR. Our results revealed a pronounced increase in Th17 and tissue-resident memory T (Trm) cells—both CD4⁺ and CD8⁺—in psoriatic lesions compared to normal skin. This cellular profile was accompanied by significantly elevated levels of IL-17A, IL-22, and TNF-α, with fold increases exceeding 5-fold for IL-17A and IL-22. Gene expression analyses demonstrated upregulation of RORC and IL17A, supporting the dominant activation of the Th17 pathway. In vitro stimulation assays identified IL-23 as the most potent inducer of IL-17 and IL-22 secretion from lesional T cells, reinforcing the centrality of the IL-23/IL-17 axis. Conversely, regulatory T cells (Tregs) were underrepresented in psoriatic plaques, indicating a failure of immune suppression. These findings collectively suggest that an imbalance between pro-inflammatory and regulatory T-cell subsets sustains chronic skin inflammation in PsA. This study provides robust immunological evidence supporting the targeting of Th17 and Trm cells as therapeutic strategies and underscores the need for treatments aimed at restoring immune equilibrium in psoriatic disease.