Differential expression of IL17 isoforms A and F in helper T Lymphocytes

Taxon: Mammal
Process: differentiation
Submitter: Aurélien Naldi

Supporting paper: Corral-Jara, Karla Fabiola and Chauvin, Camille and Abou-Jaoudé, Wassim and Grandclaudon, Maximilien and Naldi, Aurélien and Soumelis, Vassili and Thieffry, Denis (2021). Interplay between SMAD2 and STAT5A is a critical determinant of IL-17A/IL-17F differential expression. Molecular Biomedicine. 10.1186/s43556-021-00034-3

Model file(s)	Description(s)
ThIL17diff_29nov2020.zginml	GINsim file

Summary:
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, a logical model containing 82 components and 136 regulatory links was developed and calibrated with original flow cytometry data using naive CD4+ T cells in conditions inducing either IL-17A or F. Model analyses led to the identification of the transcription factors NFAT2A, STAT5A and Smad2 as key components explaining the differential expression of IL-17A and IL-17F, with STAT5A controlling IL-17F expression, and an interplay of NFAT2A, STAT5A and Smad2 controlling IL-17A expression.