Foxo1 Drives the TGF β1-Dependent Dichotomy of Th17 Cell Fates
In this study, we demonstrate that the transcription factor Foxo1 is upregulated in a TGFβ1 dose-dependent manner, serving as a critical regulator that specifically modulates the fate of pathogenic Th17 cells. Analyses in both uveitis patients and an Experimental Autoimmune Uveitis (EAU) mouse model reveal a strong correlation between disease severity and diminished Foxo1 expression levels. Ectopic expression of Foxo1 selectively attenuates IL-17A production under pathogenic Th17-inducing conditions. Moreover, enhanced Foxo1 expression, triggered by TGFβ1 signaling, is implicated in fatty acid metabolism pathways that favor non-pathogenic Th17 differentiation. Our drug screening identifies several FDA-approved compounds can upregulate Foxo1. Collectively, our findings offer evidence that Foxo1 serves as a molecular switch to specifically control pathogenic versus non-pathogenic Th17 differentiation in a TGFβ1-dependent manner. Suggest that targeting Foxo1 could be a promising therapeutic strategy for autoimmune diseases.PMID:38193891 | DOI:10.1093/jleuko/qiae004
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Mengjuan Zhang Yude Guan Meijuan Han Fandi Kong Aoyu Xu Xiaohan Jin Xiao Hu Fang Dong Nianchao Zhang Xiuping Peng Dantong Liu Yongyan Chen Ruxin Zhao Xiulei Zhu Yanan Zhang Congcong Lu Wen Hou Lei Liu Dan Li Zhihui Zhang Xiaomin Zhang Song Zhang Source Type: research
More News: Allergy & Immunology | Autoimmune Disease | Biology | Hematology | Men | Molecular Biology | Study