Assessing T-Cell Profile Shifts through IL-23 Inhibition by Guselkumab on Psoriasis.

Anti-IL-23 antibody therapies improve the underlying immunopathology of psoriasis. Immune profile dynamics after anti-IL-23 treatment and their association with the treatment response are unclear. Focusing on guselkumab, an anti-IL-23p19 antibody, we comprehensively analyzed immune cells, serum inflammatory molecules, and CD4(+) T-cell transcriptomics to identify drug effects in psoriasis. Peripheral and lesional skin blood samples were collected from 24 biologic-naïve patients at baseline and after treatment with guselkumab. We conducted FACS analysis of regulatory T cells, resident memory T cells, and dendritic cells; measured serum cytokine and chemokine levels; and analyzed RNA-sequencing data for gene expression changes in peripheral CD4(+) T cells. Guselkumab administration increased regulatory T cells and decreased resident memory T cells. Gene expression differences at baseline defined 2 groups on the basis of the treatment response: transcriptomic profile-based high responders and transcriptomic profile-based moderate responders. Expression of certain chemokines, such as CXCL1 and CXCL5, was higher in the moderate responders, suggesting their association with a lower treatment response. RNA-sequencing analysis revealed gene expression changes related to T helper 17 cells and regulatory T cell activity. We observed alterations in regulatory T cells and resident memory T cells in response to guselkumab treatment that may contribute to the long-term suppression of the IL-23-driven inflammatory pathology in psoriasis. Furthermore, baseline peripheral blood transcriptomic immune findings may predict therapeutic outcomes. The G-Grope trial was registered as jRCTs041200070 with the Japan Registry of Clinical Trials on December 8, 2020.