The following is a summary of “FOXP3+ Pro-Inflammatory T Cell: A Potential Therapeutic Target in Crohn’s Disease,” published in the April 2024 issue of Gastroenterology by Kosinsky, et al.
The incidence of Crohn’s disease (CD) is rising globally, yet the role of CD4+ cell populations in driving chronic inflammation in CD remains unclear. For a study, researchers sought to conduct a detailed transcriptional analysis of CD4+ T cells involved in chronic inflammation in CD.
Single-cell RNA-sequencing was performed on CD4+ T cells isolated from ileal biopsies of CD patients compared to healthy individuals. Cells underwent clustering analysis, followed by analysis of gene signaling networks. Differential gene expression analysis overlapped with publicly available microarray datasets. Functional in vitro studies, including an in vitro suppression assay and organoid systems, were conducted to model gene expression changes observed in CD regulatory T (Treg) cells and test predicted therapeutics.
Five distinct FOXP3+ regulatory Treg subpopulations were identified. Tregs from healthy controls served as the origin of pseudotemporal development into inflammation-associated subtypes. Proinflammatory Tregs exhibited unique responsiveness to tumor necrosis factor–α signaling, showing impaired suppressive activity in vitro and elevated cytokine response in an organoid coculture system. In silico predictions were validated as the histone deacetylase inhibitor vorinostat normalized gene expression patterns, restoring the suppressive function of FOXP3+ cells in vitro.
A novel proinflammatory FOXP3+ T cell subpopulation was identified in CD patients. A pipeline was developed to target these cells using the US Food and Drug Administration–approved drug vorinostat, suggesting a promising therapeutic approach for CD.
Reference: gastrojournal.org/article/S0016-5085(24)00009-X/fulltext