Complex interactions between the environment and the mucosal immune system underlie inflammatory bowel disease (IBD). The involved cytokine signaling pathways are modulated by a number of transcription factors, one of which is runt-related transcription factor 3 (RUNX3).
To systematically review the immune roles of RUNX3 in immune regulation, with a focus on the context of IBD.
Relevant articles and reviews were identified through a Scopus search in April 2020. Information was categorized by immune cell types, analyzed, and synthesized. IBD transcriptome datasets and FANTOM5 regulatory networks were processed in order to complement the literature review.
The available evidence on the immune roles of RUNX3 allowed for its description in twelve cell types: intraepithelial lymphocyte, Th1, Th2, Th17, Treg, double-positive T, cytotoxic T, B, dendritic, innate lymphoid, natural killer, and macrophages. In the gut, the activity of RUNX3 is multifaceted and context-dependent: it may promote homeostasis or exacerbated reactions via cytokine signaling and regulation of receptor expression. RUNX3 is mostly engaged in pathways involving ThPOK, T-bet, IFN-γ, TGF-β/IL-2Rβ, GATA/CBF-β, Smad/p300, and a number of miRNAs. RUNX3 targets relevant to IBD may include RAG1, OSM, IL17B. Moreover, in IBD RUNX3 expression correlates positively with GZMM, and negatively with IFNAR1, whereas in controls it strongly associates with TGFBR3.
Dysregulation of RUNX3, mostly in the form of deficiency, likely contributes to IBD pathogenesis. More clinical research is needed to examine RUNX3 in IBD.