慢性炎症で⼤腸に現れる「本来ない細胞」の役割を解明 −IL-22が細胞の性質を変え、REG3Aが粘膜修復を促進−

2026-05-20 東京科学大学

図. 潰瘍性大腸炎では、炎症により腸の細胞が変化し、パネート細胞様の性質をもつ細胞が出現する。これらの細胞が産生するREG3Aは、傷ついた腸の修復を助ける。

＜関連情報＞

• https://www.isct.ac.jp/ja/news/9oxitgyttidq#top
• https://www.nature.com/articles/s41467-026-71136-1

IL-22は潰瘍性大腸炎の大腸上皮にパネート細胞化生を誘導し、REG3Aを介して創傷治癒を促進する IL-22 induces Paneth cell metaplasia in the colonic epithelium of ulcerative colitis, promoting wound healing via REG3A

Tomohiro Muto,Go Ito,Hiromune Katsuda,Yui Hiraguri,Satoru Fujii,Kurara Yamamoto,Joana P. Bernardes,Finn Hinrichsen,Hitoshi Uchida,Yasuhiro Nemoto,Mayumi Kinoshita,Eri Oshina,Kouhei Yamamoto,Shuji Hibiya,Sayaka Nagata,Fenja Schuran,Shiro Yui,Penelope Pelczar,Samuel Huber,Stefan Schreiber,Philip Rosenstiel,Mamoru Watanabe & Ryuichi Okamoto
Nature Communications  Published:28 March 2026
DOI:https://doi.org/10.1038/s41467-026-71136-1  Unedited version

Abstract

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 identified IL-22, an inflammation-associated cytokine, as a key regulator that promotes PCM formation in the colonic epithelium through suppression of Notch signaling and induces REG3A expression within metaplastic niches. In vitro, we show that Reg3a directly enhances cell proliferation and promotes wound healing using mouse colonic organoids. In vivo, Reg3a^ΔIEC 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. Together, these findings support a protective role of PCM-associated REG3A in the colonic epithelium of patients with UC.