{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:19:10Z","timestamp":1789075150600,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAS-NSTDA Joint Research Project","award":["101GJHZ2024017MI"],"award-info":[{"award-number":["101GJHZ2024017MI"]}]},{"name":"Program of State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine","award":["2023QGZDSYS001"],"award-info":[{"award-number":["2023QGZDSYS001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Owing to the multifactorial nature of inflammatory bowel disease (IBD) pathogenesis, conventional two-dimensional (2D) models inadequately recapitulate the complex in vivo microenvironment. This study sought to develop an immune-microenvironment-integrated intestinal-on-a-chip model to overcome these limitations. A microfluidic chip was engineered to co-culture intestinal epithelial (Caco-2) cells and macrophages, facilitating the simulation of IBD pathological conditions for mechanistic investigations. Following inflammatory stimulation, M0 macrophages polarized into the M1 phenotype, concomitant with the upregulation of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-\u03b1), interleukin-6 (IL-6), and interleukin-1 beta (IL-1\u03b2). This induction disrupted the expression of tight junction proteins (e.g., zonula occludens-1 [ZO-1]) in Caco-2 cells, thereby compromising epithelial barrier integrity. Infliximab was used as a model drug to inhibit TNF-\u03b1 and modulate macrophage polarization within the chip, effectively rescuing impaired epithelial barrier integrity. This study establishes a reliable intestinal-on-a-chip model that recapitulates macrophage\u2013epithelial interactions in IBD, providing a robust platform for elucidating the mechanisms underlying intestinal barrier dysfunction and developing targeted therapeutic strategies.<\/jats:p>","DOI":"10.3390\/molecules31091520","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:15:02Z","timestamp":1777853702000},"page":"1520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Immune Microenvironment-Integrated Intestinal-on-a-Chip Model for Investigating Immunopathogenesis in Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"31","author":[{"given":"Shiyang","family":"Ying","sequence":"first","affiliation":[{"name":"School of Microelectronics, Shanghai University, Shanghai 200444, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhua","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianqiang","family":"Mi","sequence":"additional","affiliation":[{"name":"School of Microelectronics, Shanghai University, Shanghai 200444, China"},{"name":"Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China"},{"name":"School of Physics and Optoelectronic Engineering, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"Human Phenome Institute, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/jnr.24794","article-title":"Advances in Microfluidic In Vitro Systems for Neurological Disease Modeling","volume":"99","author":"Holloway","year":"2021","journal-title":"J. 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