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IL-22 induces Paneth cell metaplasia in the colonic epithelium of ulcerative colitis, promoting wound healing via REG3A [mouse RNA-seq]

GSE312352 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/12/03 Platform GPL24247
Summary
Paneth cell metaplasia (PCM) is a phenomenon in which Paneth cells, typically found in the small intestine, appear in the colonic epithelium of patients with ulcerative colitis (UC). Our study demonstrates that the PCM occurrence correlates with disease duration and active inflammation. Furthermore, we reveal that the inflammation-induced cytokine IL-22 suppresses Notch signaling, thereby promoting PCM formation in the colonic epithelium while simultaneously inducing REG3A expression in metaplastic niches. In vitro, we show that Reg3a directly enhances cell proliferation and promotes wound healing using mouse colonic organoids. In vivo, Reg3aΔIEC mice in both acute and chronic DSS-induced colitis models exhibit delayed wound healing. Additionally, studies conducted with patient-derived human colonic organoids revealed that REG3A administration stimulates cell proliferation and accelerates wound healing. These findings underscore a novel protective role of PCM-mediated REG3A in the colonic epithelium of patients with UC.
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Also filed as BioProject PRJNA1373151 and SRA study SRP651034. Searching any of these in the dataset finder brings you back here.

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