{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:02:09Z","timestamp":1790269329148,"version":"4.1.0"},"reference-count":106,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> is a gram-positive bacterium that may cause intestinal inflammation by secreting enterotoxins, which commonly cause food-poisoning and gastrointestinal injuries. Staphylococcal enterotoxin B (SEB) acts as a superantigen (SAg) by binding in a bivalent manner the T-cell receptor (TCR) and the costimulatory receptor CD28, thus stimulating T cells to produce large amounts of inflammatory cytokines, which may affect intestinal epithelial barrier integrity and functions. However, the role of T cell-mediated SEB inflammatory activity remains unknown. Here we show that inflammatory cytokines produced by T cells following SEB stimulation induce dysfunctions in Caco-2 intestinal epithelial cells by promoting actin cytoskeleton remodelling and epithelial cell-cell junction down-regulation. We also found that SEB-activated inflammatory T cells promote the up-regulation of epithelial-mesenchymal transition transcription factors (EMT-TFs) in a nuclear factor-\u03baB (NF-\u03baB)- and STAT3-dependent manner. Finally, by using a structure-based design approach, we identified a SEB mimetic peptide (pSEB<jats:sub>116-132<\/jats:sub>) that, by blocking the binding of SEB to CD28, dampens inflammatory-mediated dysregulation of intestinal epithelial barrier.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1365074","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T05:12:38Z","timestamp":1709701958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Targeting staphylococcal enterotoxin B binding to CD28 as a new strategy for dampening superantigen-mediated intestinal epithelial barrier dysfunctions"],"prefix":"10.3389","volume":"15","author":[{"given":"Carola","family":"Amormino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Tedeschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Fiorillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Paiardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Spallotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rosan\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta","family":"Tuosto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Kunkl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.4161\/viru.27024","article-title":"Gram-positive and gram-negative bacterial toxins in sepsis: a brief review","volume":"5","author":"Ramachandran","year":"2014","journal-title":"Virulence"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin Microbiol Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1016\/j.cell.2020.07.040","article-title":"Mortality risk profiling of staphylococcus aureus bacteremia by multi-omic serum analysis reveals early predictive and pathogenic signatures","volume":"182","author":"Wozniak","year":"2020","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00852-y","article-title":"Staphylococcus aureus host interactions and adaptation","volume":"21","author":"Howden","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2013.04.020","article-title":"Evolution of Staphylococcus aureus during human colonization and infection","volume":"21","author":"Fitzgerald","year":"2014","journal-title":"Infect Genet Evol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14070464","article-title":"Exploring the role of staphylococcus aureus in inflammatory diseases","volume":"14","author":"Chen","year":"2022","journal-title":"Toxins (Basel)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-009-0886-1","article-title":"and Sordillo, E.M. Staphylococcal enterocolitis: forgotten but not gone","volume":"55","author":"Lin","year":"2010","journal-title":"Dig Dis Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-7-21","article-title":"Methicillin-resistant Staphylococcus aureus enterocolitis sequentially complicated with septic arthritis: a case report and review of the literature","volume":"7","author":"Ogawa","year":"2014","journal-title":"BMC Res Notes"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1080\/110241501300091507","article-title":"Clinical studies of enteritis caused by methicillin-resistant Staphylococcus aureus","volume":"167","author":"Takeuchi","year":"2001","journal-title":"Eur J Surg"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21852","article-title":"Enterotoxin-producing staphylococci cause intestinal inflammation by a combination of direct epithelial cytopathy and superantigen-mediated T-cell activation","volume":"18","author":"Edwards","year":"2012","journal-title":"Inflammation Bowel Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2082177","article-title":"Staphylococcal enterotoxins","volume":"2","author":"Pinchuk","year":"2010","journal-title":"Toxins (Basel)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/toxins6051471","article-title":"and Qian, B.F. Staphylococcal enterotoxins in the etiopathogenesis of mucosal autoimmunity within the gastrointestinal tract","volume":"6","author":"Principato","year":"2014","journal-title":"Toxins (Basel)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10110459","article-title":"Bacterial superantigen toxins, CD28, and drug development","volume":"10","author":"Kaempfer","year":"2018","journal-title":"Toxins (Basel)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01388-08","article-title":"Staphylococcus aureus superantigens elicit redundant and extensive human Vbeta patterns","volume":"77","author":"Thomas","year":"2009","journal-title":"Infect Immun"},{"key":"B15","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1479-5876-6-34","article-title":"Relative quantification of TCR Vbeta-chain families by real time PCR for identification of clonal T-cell populations","volume":"6","author":"Ochsenreither","year":"2008","journal-title":"J Transl Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001149","article-title":"Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock","volume":"9","author":"Arad","year":"2011","journal-title":"PLoS Biol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1093\/infdis\/jiu556","article-title":"CD28 homodimer interface mimetic peptide acts as a preventive and therapeutic agent in models of severe bacterial sepsis and gram-negative bacterial peritonitis","volume":"211","author":"Ramachandran","year":"2015","journal-title":"J Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00942","article-title":"Staphylococcal and streptococcal superantigens trigger B7\/CD28 costimulatory receptor engagement to hyperinduce inflammatory cytokines","volume":"10","author":"Popugailo","year":"2019","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603321113","article-title":"Superantigens hyperinduce inflammatory cytokines by enhancing the B7-2\/CD28 costimulatory receptor interaction","volume":"113","author":"Levy","year":"2016","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.723689","article-title":"Binding of staphylococcal enterotoxin B (SEB) to B7 receptors triggers TCR- and CD28-mediated inflammatory signals in the absence of MHC class II molecules","volume":"12","author":"Kunkl","year":"2021","journal-title":"Front Immunol"},{"key":"B21","article-title":"Bacterial superantigen toxins induce a lethal cytokine storm by enhancing B7-2\/CD28 costimulatory receptor engagement, a critical immune checkpoint","volume":"4","author":"Kaempfer","year":"2017","journal-title":"Receptors Clin Investig"},{"key":"B22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12929-023-00941-3","article-title":"The homodimer interfaces of costimulatory receptors B7 and CD28 control their engagement and pro-inflammatory signaling","volume":"30","author":"Popugailo","year":"2023","journal-title":"J BioMed Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1170821","article-title":"Bivalent binding of staphylococcal superantigens to the TCR and CD28 triggers inflammatory signals independently of antigen presenting cells","volume":"14","author":"Kunkl","year":"2023","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2017.1343143","article-title":"The intestinal barrier: a fundamental role in health and disease","volume":"11","author":"Vancamelbeke","year":"2017","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0126-x","article-title":"and Ryu, S.H. Mechanisms regulating intestinal barrier integrity and its pathological implications","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp Mol Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.3390\/cells9081909","article-title":"The intestinal barrier and current techniques for the assessment of gut permeability","volume":"9","author":"Schoultz","year":"2020","journal-title":"Cells"},{"key":"B27","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1111\/nyas.14798","article-title":"Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival","volume":"1514","author":"Kuo","year":"2022","journal-title":"Ann N Y Acad Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.08.004","article-title":"Tight junction structure and function revisited","volume":"30","author":"Otani","year":"2020","journal-title":"Trends Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029181","article-title":"Cell-cell junctions organize structural and signaling networks","volume":"10","author":"Garcia","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.02.008","article-title":"Target specific tight junction modulators","volume":"171","author":"Brunner","year":"2021","journal-title":"Adv Drug Delivery Rev"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1017\/S0029665110001849","article-title":"A rat model of mild intestinal inflammation induced by Staphylococcus aureus enterotoxin B","volume":"69","author":"Perez-Bosque","year":"2010","journal-title":"Proc Nutr Soc"},{"key":"B32","doi-asserted-by":"publisher","first-page":"E92","DOI":"10.2527\/jas.2008-1381","article-title":"Dietary plasma proteins, the intestinal immune system, and the barrier functions of the intestinal mucosa","volume":"87","author":"Moreto","year":"2009","journal-title":"J Anim Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-1055-8","article-title":"Staphylococcus aureus enterotoxins A- and B: binding to the enterocyte brush border and uptake by perturbation of the apical endocytic membrane traffic","volume":"139","author":"Danielsen","year":"2013","journal-title":"Histochem Cell Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00436","article-title":"Basis of virulence in enterotoxin-Mediated staphylococcal food poisoning","volume":"9","author":"Fisher","year":"2018","journal-title":"Front Microbiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00864","article-title":"CD28 individual signaling up-regulates human IL-17A expression by promoting the recruitment of relA\/NF-kappaB and STAT3 transcription factors on the proximal promoter","volume":"10","author":"Kunkl","year":"2019","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.2.1062","article-title":"Epigenetic remodeling of the IL-2 and IFN-gamma loci in memory CD8 T cells is influenced by CD4 T cells","volume":"177","author":"Northrop","year":"2006","journal-title":"J Immunol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1006\/jmbi.1997.1577","article-title":"Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 A resolution: implications for superantigen recognition by MHC class II molecules and T-cell receptors","volume":"277","author":"Papageorgiou","year":"1998","journal-title":"J Mol Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/ni1170","article-title":"Crystal structure of a soluble CD28-Fab complex","volume":"6","author":"Evans","year":"2005","journal-title":"Nat Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.4049\/jimmunol.1401268","article-title":"Structure of the superantigen staphylococcal enterotoxin B in complex with TCR and peptide-MHC demonstrates absence of TCR-peptide contacts","volume":"193","author":"Rodstrom","year":"2014","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts493","article-title":"Application of asymmetric statistical potentials to antibody-protein docking","volume":"28","author":"Brenke","year":"2012","journal-title":"Bioinformatics"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1021\/ja026939x","article-title":"HADDOCK: a protein-protein docking approach based on biochemical or biophysical information","volume":"125","author":"Dominguez","year":"2003","journal-title":"J Am Chem Soc"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab336","article-title":"LZerD webserver for pairwise and multiple protein-protein docking","volume":"49","author":"Christoffer","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa849","article-title":"PyMod 3: a complete suite for structural bioinformatics in PyMOL","volume":"37","author":"Janson","year":"2021","journal-title":"Bioinformatics"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01270","article-title":"Cytokine tuning of intestinal epithelial function","volume":"9","author":"Andrews","year":"2018","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10565-005-0085-6","article-title":"The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics","volume":"21","author":"Sambuy","year":"2005","journal-title":"Cell Biol Toxicol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2022.101314","article-title":"Evaluation of Caco-2 and human intestinal epithelial cells as in vitro models of colonic and small intestinal integrity","volume":"31","author":"Lopez-Escalera","year":"2022","journal-title":"Biochem Biophys Rep"},{"key":"B48","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12964-021-00713-2","article-title":"The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems","volume":"19","author":"Leggett","year":"2021","journal-title":"Cell Commun Signal"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12095","article-title":"EMT and inflammation: inseparable actors of cancer progression","volume":"11","author":"Suarez-Carmona","year":"2017","journal-title":"Mol Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758","article-title":"Molecular mechanisms of epithelial-mesenchymal transition","volume":"15","author":"Lamouille","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085345","article-title":"Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene","volume":"9","author":"Al-Sadi","year":"2014","journal-title":"PLoS One"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.09.001","article-title":"TNF-alpha modulation of intestinal epithelial tight junction barrier is regulated by ERK1\/2 activation of Elk-1","volume":"183","author":"Al-Sadi","year":"2013","journal-title":"Am J Pathol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061944","article-title":"Amelioration of IFN-gamma and TNF-alpha-induced intestinal epithelial barrier dysfunction by berberine via suppression of MLCK-MLC phosphorylation signaling pathway","volume":"8","author":"Cao","year":"2013","journal-title":"PLoS One"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700152","article-title":"IL-22 increases permeability of intestinal epithelial tight junctions by enhancing claudin-2 expression","volume":"199","author":"Wang","year":"2017","journal-title":"J Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.590964","article-title":"CD28 autonomous signaling orchestrates IL-22 expression and IL-22-regulated epithelial barrier functions in human T lymphocytes","volume":"11","author":"Kunkl","year":"2020","journal-title":"Front Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/28101","article-title":"Three-dimensional structure of the Stat3beta homodimer bound to DNA","volume":"394","author":"Becker","year":"1998","journal-title":"Nature"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209066","article-title":"Effects of IKK inhibitor PS1145 on NF-kappaB function, proliferation, apoptosis and invasion activity in prostate carcinoma cells","volume":"25","author":"Yemelyanov","year":"2006","journal-title":"Oncogene"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609757104","article-title":"Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity","volume":"104","author":"Siddiquee","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707429200","article-title":"Twist is transcriptionally induced by activation of STAT3 and mediates STAT3 oncogenic function","volume":"283","author":"Cheng","year":"2008","journal-title":"J Biol Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.295964","article-title":"Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition","volume":"287","author":"Xiong","year":"2012","journal-title":"J Biol Chem"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.114","article-title":"MUC1-C oncoprotein activates the ZEB1\/miR-200c regulatory loop and epithelial-mesenchymal transition","volume":"33","author":"Rajabi","year":"2014","journal-title":"Oncogene"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2737","article-title":"Cisplatin-selected resistance is associated with increased motility and stem-like properties via activation of STAT3\/Snail axis in atypical teratoid\/rhabdoid tumor cells","volume":"6","author":"Liu","year":"2015","journal-title":"Oncotarget"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169622","article-title":"NF-kappaB is involved in the regulation of EMT genes in breast cancer cells","volume":"12","author":"Pires","year":"2017","journal-title":"PLoS One"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1097\/01.MIB.0000437616.37000.41","article-title":"and Durum, S.K. Targeting interleukins for the treatment of inflammatory bowel disease-what lies beyond anti-TNF therapy","volume":"20","author":"McLean","year":"2014","journal-title":"Inflammation Bowel Dis"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071670","article-title":"The role of inflammatory cytokines in the pathogenesis of colorectal carcinoma-recent findings and review","volume":"10","author":"Borowczak","year":"2022","journal-title":"Biomedicines"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2012.04.008","article-title":"Mechanisms of tumor necrosis factor-alpha-induced leaks in intestine epithelial barrier","volume":"59","author":"He","year":"2012","journal-title":"Cytokine"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1038\/s41598-018-38322-8","article-title":"Modulation of intestinal epithelial permeability by plasma from patients with crohn's disease in a three-dimensional cell culture model","volume":"9","author":"Xu","year":"2019","journal-title":"Sci Rep"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056664","article-title":"Epithelial-mesenchymal transition (EMT) induced by TNF-alpha requires AKT\/GSK-3beta-mediated stabilization of snail in colorectal cancer","volume":"8","author":"Wang","year":"2013","journal-title":"PLoS One"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1159\/000472367","article-title":"Rebeccamycin attenuates TNF-alpha-induced intestinal epithelial barrier dysfunction by inhibiting myosin light chain kinase production","volume":"41","author":"Watari","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62264-X","article-title":"and Turner, J.R. Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression","volume":"166","author":"Wang","year":"2005","journal-title":"Am J Pathol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-017-1167-5","article-title":"Lignosulfonic acid attenuates NF-kappaB activation and intestinal epithelial barrier dysfunction induced by TNF-alpha\/IFN-gamma in Caco-2 cells","volume":"72","author":"Matsuhisa","year":"2018","journal-title":"J Nat Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00856-y","article-title":"Targeting IL-6 trans-signalling: past, present and future prospects","volume":"23","author":"Rose-John","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.238147","article-title":"Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium","volume":"286","author":"Suzuki","year":"2011","journal-title":"J Biol Chem"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076650","article-title":"Src-FAK signaling mediates interleukin 6-induced HCT116 colorectal cancer epithelial-mesenchymal transition","volume":"24","author":"Huang","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192195","article-title":"The role of IL-22 in intestinal health and disease","volume":"217","author":"Keir","year":"2020","journal-title":"J Exp Med"},{"key":"B77","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.chom.2017.05.009","article-title":"IL-22 upregulates epithelial claudin-2 to drive diarrhea and enteric pathogen clearance","volume":"21","author":"Tsai","year":"2017","journal-title":"Cell Host Microbe"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.656047","article-title":"Reprogramming intestinal epithelial cell polarity by interleukin-22","volume":"8","author":"Delbue","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5234-x","article-title":"and sun, M.J. IL-17A promotes initiation and development of intestinal fibrosis through EMT","volume":"63","author":"Zhang","year":"2018","journal-title":"Dig Dis Sci"},{"key":"B80","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41580-018-0080-4","article-title":"and Weinberg, R.A. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer","volume":"20","author":"Dongre","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41580-021-00442-x","article-title":"and Goodall, G.J. The many regulators of epithelial-mesenchymal transition","volume":"23","author":"Bracken","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/35000025","article-title":"The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression","volume":"2","author":"Cano","year":"2000","journal-title":"Nat Cell Biol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.11.151","article-title":"Twist is a transcriptional repressor of E-cadherin gene expression in breast cancer","volume":"367","author":"Vesuna","year":"2008","journal-title":"Biochem Biophys Res Commun"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00260-X","article-title":"The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion","volume":"7","author":"Comijn","year":"2001","journal-title":"Mol Cell"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.102","article-title":"ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI\/SNF chromatin-remodeling protein BRG1","volume":"29","author":"Sanchez-Tillo","year":"2010","journal-title":"Oncogene"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0263","article-title":"ZIP4 promotes pancreatic cancer progression by repressing ZO-1 and claudin-1 through a ZEB1-dependent transcriptional mechanism","volume":"24","author":"Liu","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0132710","article-title":"Inflammation mediated metastasis: immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells","volume":"10","author":"Cohen","year":"2015","journal-title":"PLoS One"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2014.1000083","article-title":"CD4(+) T cells potently induce epithelial-mesenchymal-transition in premalignant and Malignant pancreatic ductal epithelial cells-novel implications of CD4(+) T cells in pancreatic cancer development","volume":"4","author":"Goebel","year":"2015","journal-title":"Oncoimmunology"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-023-07972-8","article-title":"Role of interleukins in inflammation-mediated tumor immune microenvironment modulation in colorectal cancer pathogenesis","volume":"68","author":"Jain","year":"2023","journal-title":"Dig Dis Sci"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0066-7","article-title":"Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer","volume":"18","author":"Jones","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158334","article-title":"The role of the IL-6 cytokine family in epithelial-mesenchymal plasticity in cancer progression","volume":"22","author":"Abaurrea","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112123","article-title":"Interleukin-22: immunobiology and pathology","volume":"33","author":"Dudakov","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406413200","article-title":"Alternative activation of STAT1 and STAT3 in response to interferon-gamma","volume":"279","author":"Qing","year":"2004","journal-title":"J Biol Chem"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2014.05.004","article-title":"Regulation of NF-kappaB by TNF family cytokines","volume":"26","author":"Hayden","year":"2014","journal-title":"Semin Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028522","article-title":"Interleukin 17 family cytokines: Signaling mechanisms, biological activities, and therapeutic implications","volume":"10","author":"Monin","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2007.01.077","article-title":"Isoform selective inhibition of STAT1 or STAT3 homo-dimerization via peptidomimetic probes: structural recognition of STAT SH2 domains","volume":"17","author":"Gunning","year":"2007","journal-title":"Bioorg Med Chem Lett"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2013.4841","article-title":"A novel drug for treatment of necrotizing soft-tissue infections: A randomized clinical trial","volume":"149","author":"Bulger","year":"2014","journal-title":"JAMA Surg"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit104","article-title":"A peptide antagonist of CD28 signaling attenuates toxic shock and necrotizing soft-tissue infection induced by Streptococcus pyogenes","volume":"207","author":"Ramachandran","year":"2013","journal-title":"J Infect Dis"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1537-0","article-title":"Structural basis of assembly of the human T cell receptor-CD3 complex","volume":"573","author":"Dong","year":"2019","journal-title":"Nature"},{"key":"B100","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.str.2022.03.004","article-title":"Structural characterization of a dimerization interface in the CD28 transmembrane domain","volume":"30","author":"Wu","year":"2022","journal-title":"Structure"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1038\/srep25796","article-title":"Two common structural motifs for TCR recognition by staphylococcal enterotoxins","volume":"6","author":"Rodstrom","year":"2016","journal-title":"Sci Rep"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3390\/toxins5091531","article-title":"CD28: direct and critical receptor for superantigen toxins","volume":"5","author":"Kaempfer","year":"2013","journal-title":"Toxins (Basel)"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2017.09.028","article-title":"and Kafil, H.S. The pathogenesis of Staphylococcus aureus in autoimmune diseases","volume":"111","author":"Seyyed Mousavi","year":"2017","journal-title":"Microb Pathog"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i27.4418","article-title":"Crohn's disease complicated by intestinal infection with methicillin-resistant Staphylococcus aureus","volume":"19","author":"Bettenworth","year":"2013","journal-title":"World J Gastroenterol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.09.020","article-title":"Colonic bacterial superantigens evoke an inflammatory response and exaggerate disease in mice recovering from colitis","volume":"125","author":"Lu","year":"2003","journal-title":"Gastroenterology"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.001163","article-title":"A mouse model of Staphylococcus aureus small intestinal infection","volume":"69","author":"Larcombe","year":"2020","journal-title":"J Med Microbiol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1365074\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T05:12:42Z","timestamp":1709701962000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1365074\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,6]]},"references-count":106,"alternative-id":["10.3389\/fimmu.2024.1365074"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1365074","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,6]]},"article-number":"1365074"}}