{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:44:09Z","timestamp":1792604649489,"version":"4.5.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271878, 81971480, 8257061950"],"award-info":[{"award-number":["82271878, 81971480, 8257061950"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Technology Program for Cell Therapy of NCTIB","award":["NCTIB2023XB02006"],"award-info":[{"award-number":["NCTIB2023XB02006"]}]},{"name":"Cutting Edge Development Fund of Advanced Medical Research Institute","award":["GYY2023QY01"],"award-info":[{"award-number":["GYY2023QY01"]}]},{"name":"Major Science and Technology Innovation Project of Shandong Province","award":["2024ZLGX01"],"award-info":[{"award-number":["2024ZLGX01"]}]},{"name":"National Natural Science Foundation of China Youth Science Project","award":["NSFC82300599"],"award-info":[{"award-number":["NSFC82300599"]}]},{"DOI":"10.13039\/501100010029","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tstp20231212"],"award-info":[{"award-number":["tstp20231212"]}],"id":[{"id":"10.13039\/501100010029","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    Macrophages play a pivotal role in the pathogenesis of inflammatory bowel disease (IBD). T-cell immunoglobulin and mucin domain-containing molecule 4 (TIMD4) is involved in the regulation of tissue-resident macrophages. TIMD4 expression is elevated in colonic tissues from patients with ulcerative colitis (UC) and mice with dextran sulfate sodium (DSS)-induced colitis, but its role in IBD pathogenesis remains unclear. In this study, we found that\n                    <jats:italic>Timd4<\/jats:italic>\n                    deficiency aggravated DSS-induced colitis, accompanied by increased infiltration of monocytes into the colonic tissues. Treatment with a CCR2 antagonist attenuated colonic inflammation and reduced monocyte infiltration into colonic tissues in\n                    <jats:italic>Timd4<\/jats:italic>\n                    KO mice. Mechanistically, in vitro studies revealed that TIMD4 stabilized the LKB1-STRAD-MO25 complex via its intracellular domain, thereby activating the AMPK pathway and suppressing NF-\u03baB-dependent chemokine production in macrophages. Based on these findings, we designed a TIMD4-derived peptide and developed a macrophage-targeted nanoparticle system (T4\n                    <jats:sub>(365\u2013378)<\/jats:sub>\n                    \u2011NPs). Treatment with T4\n                    <jats:sub>(365\u2013378)<\/jats:sub>\n                    -NPs reduced P65 phosphorylation and attenuated DSS-induced colitis in mice. Treatment with either T4\n                    <jats:sub>(365\u2013378)<\/jats:sub>\n                    -NPs or the CCR2 antagonist attenuated DSS-induced colitis, and no statistically significant differences in the assessed outcomes were detected between the two groups. Administration of T4\n                    <jats:sub>(365\u2013378)<\/jats:sub>\n                    -NPs before DSS exposure also attenuated subsequent colitis. Furthermore, combining the T4\n                    <jats:sub>(365\u2013378)<\/jats:sub>\n                    \u2011NPs with anti-\u03b14\u03b27 or anti-TNF-\u03b1 antibodies produced greater improvements than either monotherapy in the DSS-induced colitis model. These findings support further preclinical evaluation of TIMD4-derived peptide delivery as a potential therapeutic approach for intestinal inflammation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3004056","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:34:45Z","timestamp":1792604085000},"page":"e3004056","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A macrophage-targeted TIMD4 Peptide-Nanoparticle attenuates colitis symptoms and monocyte recruitment in a mouse model"],"prefix":"10.1371","volume":"24","author":[{"given":"Huimin","family":"Liu","sequence":"first","affiliation":[{"name":"Shandong University","place":["Jinan, Shandong, P. R. 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