EPS deficiency aggravates intestinal mucosal inflammation and dysbiosis through disrupting macrophage polarization balance in ulcerative colitis.

BACKGROUND

Ulcerative colitis (UC) is a chronic, immune-mediated inflammatory bowel disorder, and macrophages are essential for maintaining intestinal mucosal balance during UC. Long intergenic non-coding RNA-erythroid prosurvival (lincRNA-EPS) is a novel lincRNA identified as a key inflammatory regulator. Nonetheless, the specific role of EPS in the pathogenesis of UC remains unclear.

METHODS

To investigate the contribution of EPS to intestinal inflammation, a model of colitis induced by dextran sulfate sodium (DSS) was created using both EPS gene knockout (EPS-/-) mice and wild-type (WT) mice. The impact of EPS on macrophage activities was assessed through various methods including qRT-PCR, flow cytometry, and immunofluorescence. Biopsies of the colon were collected from individuals diagnosed with UC for the purpose of EPS detection.

RESULTS

EPS-/- mice exhibited more severe intestinal mucosal inflammation after DSS treatment, which was characterized by an increase in inflammatory cell infiltration, suppressed recovery of tight junction proteins and microbiota balance. EPS inhibits M1 macrophage polarization while promoting M2 macrophage polarization both in vitro and in vivo. The expression of EPS was found to be decreased in the inflamed mucosa and peripheral blood mononuclear cell (PBMC) of individuals suffering from UC, showing a negative correlation with the level of disease activity.

CONCLUSIONS

This study revealed a novel function of EPS in macrophages in regulating the M1/M2 balance, inflammation, and gut microbiota during the pathological process of UC, and targeting EPS may represent a promising therapeutic approach for UC.