{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:27:19Z","timestamp":1786116439516,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kindai University Research Enhancement","award":["KD2405"],"award-info":[{"award-number":["KD2405"]}]},{"name":"Kindai University Research Enhancement","award":["KD2505"],"award-info":[{"award-number":["KD2505"]}]},{"name":"Kindai University Research Enhancement","award":["KD2605"],"award-info":[{"award-number":["KD2605"]}]},{"award":["KD2405"],"award-info":[{"award-number":["KD2405"]}],"id":[{"id":"https:\/\/ror.org\/05kt9ap64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["KD2505"],"award-info":[{"award-number":["KD2505"]}],"id":[{"id":"https:\/\/ror.org\/05kt9ap64","id-type":"ROR","asserted-by":"publisher"}]},{"award":["KD2605"],"award-info":[{"award-number":["KD2605"]}],"id":[{"id":"https:\/\/ror.org\/05kt9ap64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Inflammatory bowel diseases (IBDs), chronic inflammatory disorders of the gastrointestinal tract, are classified into Crohn\u2019s disease (CD) and ulcerative colitis (UC). Despite differing clinical manifestations, both CD and UC share a common immunopathogenesis, involving excessive production of proinflammatory cytokines by macrophages and dendritic cells. Tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-12 (IL-12), and IL-23 are prototypical proinflammatory cytokines associated with CD and UC development, and biologics targeting these cytokines are widely used for treating patients with IBD. Antibodies (Abs) against IL-12 and IL-23 decrease intestinal inflammation by binding to the soluble forms of IL-12 and IL-23, respectively. Notably, anti-TNF-\u03b1 Abs induce remission by neutralizing soluble TNF-\u03b1 as well as membrane-bound TNF-\u03b1 (mTNF-\u03b1). The binding of anti-TNF-\u03b1 Abs to mTNF-\u03b1 enables the diverse functions of IBD-specific TNF-\u03b1-inhibitors. Multiple modes of action of anti-TNF-\u03b1 Abs for IBD include complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity, apoptosis of cells expressing mTNF-\u03b1, apoptosis of lamina propria T cells, and induction of regulatory T cells and macrophages. In this article, we introduce the diverse actions of anti-TNF-\u03b1 Abs beyond TNF-\u03b1 neutralization and discuss how these unique properties of anti-TNF-\u03b1 Abs contribute to the efficient downregulation of IBD-associated inflammation.<\/jats:p>","DOI":"10.3390\/antib15040071","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:46:38Z","timestamp":1786009598000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple Modes of Action of Anti-TNF-\u03b1 Antibodies for Inflammatory Bowel Diseases Beyond TNF-\u03b1 Neutralization"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6175-8064","authenticated-orcid":false,"given":"Tomohiro","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, 1-14-1 Mihara-dai, Minami-ku, Sakai 590-0197, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4102-3474","authenticated-orcid":false,"given":"Masatoshi","family":"Kudo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, 1-14-1 Mihara-dai, Minami-ku, Sakai 590-0197, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eabq4473","DOI":"10.1126\/scitranslmed.abq4473","article-title":"Targeting cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2022","journal-title":"Sci. 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