Waiting in the wings: <i>RUNX3</i> reveals hidden depths of immune regulation with potential implications for inflammatory bowel disease

Abstract Background Complex interactions between the environment and mucosal immune system underlie inflammatory bowel disease (IBD). The involved cytokine signalling pathways are modulated by a number of transcription factors, one which is runt‐related factor 3 (RUNX3). Objective To systematically review roles RUNX3 in regulation, with focus on context IBD. Methods Relevant articles reviews were identified through Scopus search April 2020. Information was categorized cell types, analysed synthesized. IBD transcriptome data sets FANTOM5 regulatory networks processed order to complement literature review. Results available evidence allowed for its description twelve types: intraepithelial lymphocyte, Th1, Th2, Th17, Treg, double‐positive T, cytotoxic B, dendritic, innate lymphoid, natural killer macrophages. In gut, activity multifaceted context‐dependent: it may promote homeostasis or exacerbated reactions via regulation receptor expression. mostly engaged involving ThPOK, T‐bet, IFN‐γ, TGF‐β/IL‐2Rβ, GATA/CBF‐β, SMAD/p300 miRNAs. targets relevant include RAG1, OSM IL‐17B. Moreover, expression correlates positively GZMM , negatively IFNAR1 whereas controls, strongly associates TGFBR3 . Conclusions Dysregulation RUNX3, form deficiency, likely contributes pathogenesis. More clinical research needed examine