What question did this study set out to answer?

The study aims to explore the role of PUMILIO2 (Pum2) in the regulation of intestinal inflammation and its effects on macrophage-epithelial interactions.

March 21, 2026Open Access

Loss of Pum2 exacerbates colitis by disrupting macrophage–epithelial crosstalk and promoting epithelial necroptosis

XWXuefei WangUnion Hospital XHXiaoxiao HanNantong University WQWenlin QiuWuhan Union Hospital

Key Points

The study aims to explore the role of PUMILIO2 (Pum2) in the regulation of intestinal inflammation and its effects on macrophage-epithelial interactions.
Analyzed colonic tissues from ulcerative colitis patients for Pum2 expression levels.
Utilized dextran sulfate sodium (DSS) models to induce colitis in mice.
Examined the impact of Pum2 deficiency on mucosal damage and inflammation during colitis.
Pum2 expression is significantly reduced in UC patients, correlating with increased disease activity.
Pum2 deficiency leads to worsened mucosal injury in DSS-induced colitis models.
Loss of Pum2 results in enhanced macrophage hyperactivation and increased epithelial necroptosis.

Abstract

Abstract Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder characterized by persistent mucosal immune activation and compromised epithelial barrier function. In this study, we identify the RNA-binding protein PUMILIO2 (Pum2) as a previously unrecognized regulator of intestinal inflammation. Analysis of colonic tissues from UC patients revealed reduced Pum2 expression, which inversely correlated with disease activity. In dextran sulfate sodium (DSS)-induced colitis models, Pum2 deficiency exacerbated mucosal injury, accompanied by heightened macrophage inflammation. Mechanistically, Pum2 loss during colitis drives macrophage hyperactivation and TNFα-dependent epithelial necroptosis, which together intensify pathogenic macrophage–epithelial interactions and barrier breakdown. The dynamic downregulation of Pum2 in active inflammation underscores its potential as a therapeutic target for modulating macrophage–epithelial interactions and restoring intestinal barrier integrity in the context of colitis.

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