050 High-dimensional profiling of regulatory T cells in psoriasis reveals an impaired skin-homing property

Psoriasis is an inflammatory skin disease with a Th17-skewed phenotype. Evidence has suggested on the potential role of regulatory T cells(Tregs) in the pathogenesis of psoriasis. However, high-dimensional profiling of the molecular properties of psoriatic Tregs is limited. In particular, the role of skin-homing Tregs which infiltrate into the lesional skin and exert suppressive capacity has yet to be elucidated. To address this, we designed an extensive panel for mass cytometry (CyTOF) encompassing 39 markers to profile skin-homing Tregs from 32 age and sex-matched psoriatic patients and healthy controls. Furthermore, we analyzed public scRNA-seq data to expand upon our findings into the local tissue microenvironments. We discovered a decreased frequency of CLAhi CCR5+ Tregs in patients with psoriasis. CCR7 was increased and CCR4 was reduced in both total and CLAhi Treg compartments. Functional markers revealed an increased expression of CD39 in CLAhiTregs. This was consistent within the subgroups stratified by disease severity. Analysis of scRNA-seq data showed a decreased expression of skin-homing markers and relevant cell-cell interactions in Tregs from psoriatic lesional skin, reflecting diminished skin-homing properties of psoriatic Tregs. Therefore, psoriatic circulating Tregs have an impaired skin-trafficking phenotype leading to insufficient suppression of inflammation in the lesional skin, expanding upon our current understanding of the impairment of Treg-mediated immunosuppression in psoriasis.