RT Journal Article SR Electronic T1 Causal dynamical modelling predicts novel regulatory genes of FOXP3 in human regulatory T cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.13.943688 DO 10.1101/2020.02.13.943688 A1 Rucha Sawlekar A1 Stefano Magni A1 Christophe Capelle A1 Alexandre Baron A1 Ni Zeng A1 Laurent Mombaerts A1 Zuogong Yue A1 Ye Yuan A1 Feng Q. He A1 Jorge Gonçalves YR 2020 UL http://biorxiv.org/content/early/2020/02/14/2020.02.13.943688.abstract AB Regulatory T cells (Tregs), characterized as a CD4+CD25+FOXP3+ subset of T cells, are vital to the induction of immune tolerance and the maintenance of immune homeostasis. While target genes of Treg master regulator FOXP3 have been identified, the upstream regulatory machinery of FOXP3 still remains largely unknown. Here we dynamically model causal relationships among genes from available time-series genome-scale datasets, to predict direct or indirect regulatory genes of FOXP3 in human primary Tregs. From the whole genome, we selected five top ranked candidates for further experimental validation. Following knockdown, three out of the five candidates indeed showed significant effects on the mRNA expression of FOXP3. Further experiments showed that one out of these three predicted candidates, namely nuclear receptor binding factor 2 (NRBF2), also affected FOXP3 protein expression. These results open new doors to identify potential new mechanisms of immune related diseases.