AUTHOR=Chen Yiqiao , Tontini Chiara , Tosi Isabella , Barker Jonathan N. , Di Meglio Paola , Griffiths Christopher E. M. , Bahri Rajia , Bulfone-Paus Silvia TITLE=Circulating CD8 T cells from patients with mild-to-moderate psoriasis are functionally impaired JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1585378 DOI=10.3389/fimmu.2025.1585378 ISSN=1664-3224 ABSTRACT=BackgroundPsoriasis is a systemic, immune-mediated, inflammatory skin disease in which T cells have been found to play a significant role. The phenotypic and functional properties of circulating CD8 T cells in the pathogenesis of the disease are still ill-defined.ObjectiveThis study aimed to assess changes in the phenotype, activation status and mediator release of CD8 T cells in the peripheral blood of patients with mild-to-moderate psoriasis.MethodsPeripheral blood mononuclear cells from patients with mild-to-moderate psoriasis and healthy individuals were used to investigate the CD8 T cell immune phenotype and mediator release upon in vitro TCR-independent (phorbol 12-myristate 13-acetate (PMA) plus ionomycin (ION)) or TCR-dependent (anti-CD3/CD28) activation by flow cytometry.ResultsPatients with psoriasis exhibited reduced circulating CD8 memory T cell frequency compared to healthy controls. Additionally, although CD8 T cell subsets showed similar levels of the skin homing marker CCR4, they demonstrated a significant upregulation of B- and T-lymphocyte attenuator (BTLA) expression compared to healthy individuals. Upon CD8 T cell activation, IL-17A and IL-17F were expressed at low and comparable levels in psoriasis patients and healthy controls. In contrast, CD69, IFNγ, and Granzyme B were significantly decreased in anti-CD3/CD28-activated CD8 T cell subsets. PASI scores positively correlated with IFNγ-producing CD8 T memory cells and negatively with TNF-producing CD8- T cell subsets.ConclusionPatients with mild-to-moderate psoriasis showed a significant decrease in CD8 T memory cells and reduced release of cytotoxic mediators by CD8 T cells. Thus, this indicates that psoriasis impacts the functionality of circulating CD8 T cells.