{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:20:57Z","timestamp":1789176057908,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Inflammatory bowel disease (IBD), such as Crohn\u2019s disease and ulcerative colitis, is a complex disease involving genetic, immune, and microbiological factors. A variety of animal models of IBD have been developed to study the pathogenesis of human IBD, but there is no model that can fully represent the complexity of IBD. In this study, we established two acute enteritis models by oral 3% DSS or intraperitoneal injection of anti-CD3 antibody, and two chronic enteritis models by feeding 3 cycles of 1.5% DSS or 3 months of the high-fat diet, respectively, and then examined the clinical parameters, histological changes, and cytokine expression profiles after the successful establishment of the models. Our results indicated that in 3% DSS-induced acute enteritis, the colorectal injury was significantly higher than that of the small intestine, while in anti-CD3 antibody-induced acute enteritis, the small intestine injury was significantly higher than that of colorectal damage. Besides, in the 1.5% DSS-induced chronic enteritis, the damage was mainly concentrated in the colorectal, while the damage caused by long-term HFD-induced chronic enteritis was more focused on the small intestine. Therefore, our work provides a reference for selecting appropriate models when conducting research on factors related to the pathogenesis of IBD or evaluating the potential diagnosis and treatment possibilities of pharmaceuticals.<\/jats:p>","DOI":"10.3389\/fimmu.2021.727664","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T07:15:03Z","timestamp":1640157303000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Characterization and Analysis of the Temporal and Spatial Dynamic of Several Enteritis Modeling Methodologies"],"prefix":"10.3389","volume":"12","author":[{"given":"Huangru","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqian","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huisong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqin","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Chun","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06005","article-title":"Unravelling the Pathogenesis of Inflammatory Bowel Disease","volume":"448","author":"Xavier","year":"2007","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.11.059","article-title":"Microbial Influences in Inflammatory Bowel Diseases","volume":"134","author":"Sartor","year":"2008","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.56.8.2101-2108.1988","article-title":"Systemic Uptake and Intestinal Inflammatory Effects of Luminal Bacterial Cell Wall Polymers in Rats With Acute Colonic Injury","volume":"56","author":"Sartor","year":"1988","journal-title":"Infect Immun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S0016-5085(89)80079-4","article-title":"Hapten-Induced Model of Chronic Inflammation and Ulceration in the Rat Colon","volume":"96","author":"Morris","year":"1989","journal-title":"Gastroenterology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/0016-5085(90)90290-h","article-title":"A Novel Method in the Induction of Reliable Experimental Acute and Chronic Ulcerative Colitis in Mice","volume":"98","author":"Okayasu","year":"1990","journal-title":"Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)80067-o","article-title":"Ulcerative Colitis-Like Disease in Mice With a Disrupted Interleukin-2 Gene","volume":"75","author":"Sadlack","year":"1993","journal-title":"Cell"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)80068-p","article-title":"Interleukin-10-Deficient Mice Develop Chronic Enterocolitis","volume":"75","author":"Kuhn","year":"1993","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)80069-q","article-title":"Spontaneous Development of Inflammatory Bowel Disease in T Cell Receptor Mutant Mice","volume":"75","author":"Mombaerts","year":"1993","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5285.262","article-title":"Impaired Defense of Intestinal Mucosa in Mice Lacking Intestinal Trefoil Factor","volume":"274","author":"Mashimo","year":"1996","journal-title":"Science"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80038-2","article-title":"Impaired on\/Off Regulation of TNF Biosynthesis in Mice Lacking TNF AU-Rich Elements: Implications for Joint and Gut-Associated Immunopathologies","volume":"10","author":"Kontoyiannis","year":"1999","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90512-d","article-title":"Spontaneous Inflammatory Disease in Transgenic Rats Expressing HLA-B27 and Human Beta 2m: An Animal Model of HLA-B27-Associated Human Disorders","volume":"63","author":"Hammer","year":"1990","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.162.4.1884","article-title":"Cutting Edge: Chronic Intestinal Inflammation in STAT-4 Transgenic Mice: Characterization of Disease and Adoptive Transfer by TNF- Plus IFN-Gamma-Producing CD4+ T Cells That Respond to Bacterial Antigens","volume":"162","author":"Wirtz","year":"1999","journal-title":"J\u00a0Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1023\/a:1027322631036","article-title":"The Serum Factor From Patients With Ulcerative Colitis That Induces T Cell Proliferation in the Mouse Thymus is Interleukin-7","volume":"17","author":"Watanabe","year":"1997","journal-title":"J Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.6.855","article-title":"CD4+ T Cells Reactive to Enteric Bacterial Antigens in Spontaneously Colitic C3H\/HeJBir Mice: Increased T Helper Cell Type 1 Response and Ability to Transfer Disease","volume":"187","author":"Cong","year":"1998","journal-title":"J Exp Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1053\/j.gastro.2005.05.032","article-title":"Activation of A2A Adenosine Receptor Attenuates Intestinal Inflammation in Animal Models of Inflammatory Bowel Disease","volume":"129","author":"Odashima","year":"2005","journal-title":"Gastroenterology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80110-7","article-title":"Autoimmune Intestinal Pathology Induced by Hsp60-Specific CD8 T Cells","volume":"11","author":"Steinhoff","year":"1999","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90599-5","article-title":"Experimental Models of Inflammatory Bowel Disease","volume":"109","author":"Elson","year":"1995","journal-title":"Gastroenterology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1292\/jvms.61.67","article-title":"Tissue Distribution of Dextran Sulfate Sodium (DSS) in the Acute Phase of Murine DSS-Induced Colitis","volume":"61","author":"Kitajima","year":"1999","journal-title":"J Vet Med Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"15 25 11","DOI":"10.1002\/0471142735.im1525s104","article-title":"Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice","volume":"104","author":"Chassaing","year":"2014","journal-title":"Curr Protoc Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2015.01.006","article-title":"Experimental Models of Inflammatory Bowel Diseases","volume":"1","author":"Kiesler","year":"2015","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830200308","article-title":"Cytokine-Related Syndrome Following Injection of Anti-CD3 Monoclonal Antibody: Further Evidence for Transient In Vivo T Cell Activation","volume":"20","author":"Ferran","year":"1990","journal-title":"Eur J Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1097\/00007890-199004000-00009","article-title":"In Vivo Cell Activation Following OKT3 Administration. Systemic Cytokine Release and Modulation by Corticosteroids","volume":"49","author":"Chatenoud","year":"1990","journal-title":"Transplantation"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15695","article-title":"T Cell Activation Causes Diarrhea by Increasing Intestinal Permeability and Inhibiting Epithelial Na+\/K+-ATPase","volume":"110","author":"Musch","year":"2002","journal-title":"J Clin Invest"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24970","article-title":"Epithelial Myosin Light Chain Kinase-Dependent Barrier Dysfunction Mediates T Cell Activation-Induced Diarrhea In Vivo","volume":"115","author":"Clayburgh","year":"2005","journal-title":"J Clin Invest"},{"key":"B25","article-title":"Clinicopathologic Study of Dextran Sulfate Sodium Experimental Murine Colitis","volume":"69","author":"Cooper","year":"1993","journal-title":"Lab Invest"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012191","article-title":"High-Fat Diet: Bacteria Interactions Promote Intestinal Inflammation Which Precedes and Correlates With Obesity and Insulin Resistance in Mouse","volume":"5","author":"Ding","year":"2010","journal-title":"PloS One"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047713","article-title":"High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway","volume":"7","author":"Kim","year":"2012","journal-title":"PloS One"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2011.07.002","article-title":"Diet-Induced Obesity Elevates Colonic TNF-Alpha in Mice and is Accompanied by an Activation of Wnt Signaling: A Mechanism for Obesity-Associated Colorectal Cancer","volume":"23","author":"Liu","year":"2012","journal-title":"J Nutr Biochem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2011.44","article-title":"Dietary Intake and Risk of Developing Inflammatory Bowel Disease: A Systematic Review of the Literature","volume":"106","author":"Hou","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/srep28990","article-title":"High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation That Is Reversed by IL-22","volume":"6","author":"Gulhane","year":"2016","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.044","article-title":"Chemically Induced Mouse Models of Acute and Chronic Intestinal Inflammation","volume":"12","author":"Wirtz","year":"2017","journal-title":"Nat Protoc"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000401","article-title":"Heterogeneous Nuclear Ribonucleoprotein A1 Improves the Intestinal Injury by Regulating Apoptosis Through Trefoil Factor 2 in Mice With Anti-CD3-Induced Enteritis","volume":"21","author":"Ando","year":"2015","journal-title":"Inflamm Bowel Dis"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/BF01303184","article-title":"Treatment of Dextran Sulfate Sodium-Induced Murine Colitis by Intracolonic Cyclosporin","volume":"38","author":"Murthy","year":"1993","journal-title":"Dig Dis Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090093","article-title":"Treatment With a Novel Chemokine-Binding Protein or Eosinophil Lineage-Ablation Protects Mice From Experimental Colitis","volume":"175","author":"Vieira","year":"2009","journal-title":"Am J Pathol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060594","article-title":"Role of Blood- and Tissue-Associated Inducible Nitric-Oxide Synthase in Colonic Inflammation","volume":"170","author":"Krieglstein","year":"2007","journal-title":"Am J Pathol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-021-01814-y","article-title":"Mucosal and Faecal Neutrophil Gelatinase-Associated Lipocalin as Potential Biomarkers for Collagenous Colitis","volume":"56","author":"Bakke","year":"2021","journal-title":"J Gastroenterol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/s40168-021-01161-3","article-title":"Utilizing a Reductionist Model to Study Host-Microbe Interactions in Intestinal Inflammation","volume":"9","author":"Tsou","year":"2021","journal-title":"Microbiome"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01081","article-title":"The Gut Microbiota in Immune-Mediated Inflammatory Diseases","volume":"7","author":"Forbes","year":"2016","journal-title":"Front Microbiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9948","article-title":"Gene-Microbiota Interactions Contribute to the Pathogenesis of Inflammatory Bowel Disease","volume":"352","author":"Chu","year":"2016","journal-title":"Science"},{"key":"B40","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.tibtech.2015.06.011","article-title":"Proteobacteria: Microbial Signature of Dysbiosis in Gut Microbiota","volume":"33","author":"Shin","year":"2015","journal-title":"Trends Biotechnol"},{"key":"B41","first-page":"22","article-title":"Specific Type IV Phosphodiesterase Inhibitor Rolipram Mitigates Experimental Colitis in Mice","volume":"292","author":"Hartmann","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"B42","first-page":"99","article-title":"Adenosine Kinase Inhibitor GP515 Improves Experimental Colitis in Mice","volume":"296","author":"Siegmund","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9440(10)64259-9","article-title":"Hyperosmotic Stress Induces Nuclear factor-kappaB Activation and Interleukin-8 Production in Human Intestinal Epithelial Cells","volume":"161","author":"Nemeth","year":"2002","journal-title":"Am J Pathol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90296.2008","article-title":"Hyperosmotic Stress Contributes to Mouse Colonic Inflammation Through the Methylation of Protein Phosphatase 2A","volume":"295","author":"Schwartz","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(94)90614-9","article-title":"Cytokines in Intestinal Inflammation: Pathophysiological and Clinical Considerations","volume":"106","author":"Sartor","year":"1994","journal-title":"Gastroenterology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-304119","article-title":"Western Diet Induces Dysbiosis With Increased E Coli in CEABAC10 Mice, Alters Host Barrier Function Favouring AIEC Colonisation","volume":"63","author":"Martinez-Medina","year":"2014","journal-title":"Gut"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2010.06332.x","article-title":"Western-Style Diets Induce Macrophage Infiltration and Contribute to Colitis-Associated Carcinogenesis","volume":"25","author":"Kim","year":"2010","journal-title":"J Gastroenterol Hepatol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032084","article-title":"Dextran Sodium Sulfate (DSS) Induces Colitis in Mice by Forming Nano-Lipocomplexes With Medium-Chain-Length Fatty Acids in the Colon","volume":"7","author":"Laroui","year":"2012","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071661","article-title":"High Fat Diet Accelerates Pathogenesis of Murine Crohn\u2019s Disease-Like Ileitis Independently of Obesity","volume":"8","author":"Gruber","year":"2013","journal-title":"PloS One"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065878","article-title":"High Beta-Palmitate Fat Controls the Intestinal Inflammatory Response and Limits Intestinal Damage in Mucin Muc2 Deficient Mice","volume":"8","author":"Lu","year":"2013","journal-title":"PloS One"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3945\/jn.113.174615","article-title":"High-Fat Diet-Induced Obesity Exacerbates Inflammatory Bowel Disease in Genetically Susceptible Mdr1a-\/- Male Mice","volume":"143","author":"Paik","year":"2013","journal-title":"J Nutr"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.727664\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T18:56:59Z","timestamp":1674154619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.727664\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":51,"alternative-id":["10.3389\/fimmu.2021.727664"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.727664","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]},"article-number":"727664"}}