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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Vaccines and Molecular Therapeutics

CU104, a novel barrier function enhancer, improves colitis via modulation of barrier function and immune cell recruitment

Provisionally accepted
I Seul ParkI Seul Park1Ji Hyung KimJi Hyung Kim1Dongyeop KimDongyeop Kim2Ye Won KimYe Won Kim1Yoojin ShinYoojin Shin1Ki Beom KimKi Beom Kim1Haiying ZhangHaiying Zhang3TAE IL KIMTAE IL KIM1Seung Won KimSeung Won Kim1*Young-guen KwonYoung-guen Kwon2*Jae Hee CheonJae Hee Cheon4*
  • 1Yonsei University College of Medicine, Seodaemun-gu, Republic of Korea
  • 2Yonsei University, Seodaemun-gu, Republic of Korea
  • 3Curacle Co Ltd, Seocho-gu, Republic of Korea
  • 4College of Medicine, Yonsei University, Seoul, Republic of Korea

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Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic and relapsing condition with complex pathogenesis and limited therapeutic options. The efficacy of CU104, a novel blocker of endothelial dysfunction, in IBD models is poorly understood. Moreover, its precise cellular or molecular mechanisms in colitis remain unknown. Methods: To evaluate the therapeutic potential of CU104, we tested CU104 in two colitis models: dinitrobenzene sulfonic acid (DNBS)–induced colitis in wild-type mice and dextran sodium sulfate (DSS)–challenged colitis in IL-10 knockout mice. Additionally, we used Caco-2, HCT-116, and HT-29 cells to assess CU104 effects on intestinal barrier function (FITC-dextran permeability and TEER), inflammatory signaling (reporter assays), actin dynamics, and gene expression (gene expression profiling and immune assays). Results: CU104 demonstrated potent suppressive effects on innate immune responses, intestinal and vascular barrier dysfunctions, and immune cell recruitment in these colitis models. Furthermore, CU104 inhibited the activation of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and interferon regulatory factor, as well as the ezrin/radixin/moesin (ERM) signaling pathway, both in vitro and in vivo, by modulating actin dynamics. Consistent with these findings, CU104 improved the functions of vascular and intestinal barriers and regulated immune cell recruitment during inflammation. Conclusions: Collectively, our findings demonstrate that CU104 can regulate actin dynamics and inflammatory signaling pathways, highlighting potential therapeutic targets for IBD.

Keywords: actin dynamics, Barrier function, immune cell recruitment, interferon regulatory factor, interleukin 10

Received: 15 Dec 2025; Accepted: 12 Feb 2026.

Copyright: © 2026 Park, Kim, Kim, Kim, Shin, Kim, Zhang, KIM, Kim, Kwon and Cheon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Seung Won Kim
Young-guen Kwon
Jae Hee Cheon

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material