Interplay between SMAD2 and STAT5A is a critical determinant of IL-17A/IL-17F differential expression.

ABSTRACT: Interleukins (IL)-17A and F are critical cytokines in anti-microbial immunity but also contribute to auto-immune pathologies. Recent evidence suggests that they may be differentially produced by T-helper (Th) cells, but the underlying mechanisms remain unknown. To address this question, we built a regulatory graph integrating all reported upstream regulators of IL-17A and F, completed by ChIP-seq data analyses. The resulting regulatory graph encompasses 82 components and 136 regulatory links. The graph was then supplemented by logical rules calibrated with original flow cytometry data using naive CD4⁺ T cells, in conditions inducing IL-17A or IL-17F. The model displays specific stable states corresponding to virtual phenotypes explaining IL-17A and IL-17F differential regulation

SUBMITTER: Corral-Jara KF 

PROVIDER: S-EPMC8607379 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature