{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:31:25Z","timestamp":1760146285904,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["RO1 DK067592"],"award-info":[{"award-number":["RO1 DK067592"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 1 diabetes (T1D) is an autoimmune disease that is caused by autoreactive T cell-mediated destruction of insulin-producing \u03b2 cells in the pancreatic islets. Although naive autoreactive T cells are initially primed by islet antigens in pancreas-draining lymph nodes (pan-LNs), the adhesion molecules that recruit T cells into pan-LNs are unknown. We show that high endothelial venules in pan-LNs of young nonobese diabetic mice have a unique adhesion molecule profile that includes strong expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Anti-MAdCAM-1 antibody blocked more than 80% of the migration of naive autoreactive CD4+ T cells from blood vessels into pan-LNs. Transient blockade of MAdCAM-1 in young nonobese diabetic mice led to increased numbers of autoreactive regulatory CD4+ T cells in pan-LNs and pancreas and to long-lasting protection from T1D. These results indicate the importance of MAdCAM-1 in the development of T1D and suggest MAdCAM-1 as a potential therapeutic target for treating T1D.<\/jats:p>","DOI":"10.3390\/ijms252111350","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T06:11:25Z","timestamp":1729577485000},"page":"11350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mucosal Addressin Cell Adhesion Molecule-1 Mediates T Cell Migration into Pancreas-Draining Lymph Nodes for Initiation of the Autoimmune Response in Type 1 Diabetes"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-0910","authenticated-orcid":false,"given":"Yankui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Tianjin Medical University Second Hospital, Tianjin 300211, China"},{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA"},{"name":"Department of Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel C.","family":"Gunderson","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA"},{"name":"Department of Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45219, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5375-4557","authenticated-orcid":false,"given":"Wenjia","family":"Ai","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA"},{"name":"Department of Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4418-4588","authenticated-orcid":false,"given":"Fanru","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA"},{"name":"Department of Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2857-7464","authenticated-orcid":false,"given":"Baohui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA"},{"name":"Department of Surgery, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara A.","family":"Michie","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/nri1222","article-title":"Homing and cellular traffic in lymph nodes","volume":"3","author":"Mempel","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/0092-8674(91)90279-8","article-title":"Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity","volume":"67","author":"Butcher","year":"1991","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0092-8674(94)90337-9","article-title":"Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm","volume":"76","author":"Springer","year":"1994","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12604","DOI":"10.1073\/pnas.91.26.12604","article-title":"A predominant role of integrin alpha 4 in the spontaneous development of autoimmune diabetes in nonobese diabetic mice","volume":"91","author":"Yang","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/1074-7613(95)90162-0","article-title":"Distinct roles of L-selectin and integrins alpha 4 beta 7 and LFA-1 in lymphocyte homing to Peyer\u2019s patch-HEV in situ: The multistep model confirmed and refined","volume":"3","author":"Bargatze","year":"1995","journal-title":"Immunity"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/349796a0","article-title":"ELAM-1 is an adhesion molecule for skin-homing T cells","volume":"349","author":"Picker","year":"1991","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1084\/jem.20010685","article-title":"Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin\/PNAd, a4b1 integrin\/VCAM-1 and LFA-1 adhesion pathways","volume":"197","author":"Xu","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5969","DOI":"10.4049\/jimmunol.152.12.5969","article-title":"Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice","volume":"152","author":"Faveeuw","year":"1994","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/331041a0","article-title":"A tissue-specific endothelial cell molecule involved in lymphocyte homing","volume":"331","author":"Streeter","year":"1988","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1083\/jcb.107.5.1853","article-title":"Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes","volume":"107","author":"Streeter","year":"1988","journal-title":"J. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/1521-4141(200211)32:11<3029::AID-IMMU3029>3.0.CO;2-9","article-title":"Mucosal addressin expression and binding-interactions with naive lymphocytes vary among the cranial, oral, and nasal-associated lymphoid tissues","volume":"32","author":"Csencsits","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.jaut.2010.04.002","article-title":"Alpha4beta7 integrin\/MAdCAM-1 adhesion pathway is crucial for B cell migration into pancreatic lymph nodes in nonobese diabetic mice","volume":"35","author":"Xu","year":"2010","journal-title":"J. Autoimmun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1465-9921-10-97","article-title":"Expression of endothelia and lymphocyte adhesion molecules in bronchus-associated lymphoid tissue (BALT) in adult human lung","volume":"10","author":"Kawamata","year":"2009","journal-title":"Respir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1399-0039.2005.00434.x","article-title":"Mechanisms of lymphocyte migration in autoimmune disease","volume":"66","author":"Norman","year":"2005","journal-title":"Tissue Antigens"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1084\/jem.20011353","article-title":"Pancreatic lymph nodes are required for priming of beta cell reactive T cells in NOD mice","volume":"196","author":"Gagnerault","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1084\/jem.189.2.331","article-title":"Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes","volume":"189","author":"Hoglund","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/ni1289","article-title":"Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice","volume":"7","author":"Tang","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1084\/jem.20030966","article-title":"Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model","volume":"198","author":"Turley","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.4049\/jimmunol.168.3.1466","article-title":"In situ beta cell death promotes priming of diabetogenic CD8 T lymphocytes","volume":"168","author":"Zhang","year":"2002","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.0105-2896.2005.00248.x","article-title":"The stages of type 1A diabetes: 2005","volume":"204","author":"Gianani","year":"2005","journal-title":"Immunol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1146\/annurev.immunol.23.021704.115643","article-title":"The NOD mouse: A model of immune dysregulation","volume":"23","author":"Anderson","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1093\/intimm\/7.12.1905","article-title":"Homing of lymphocytes into islets of Langerhans in prediabetic non-obese diabetic mice is not restricted to autoreactive T cells","volume":"7","author":"Faveeuw","year":"1995","journal-title":"Int. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1172\/JCI116859","article-title":"Vascular addressins are induced on islet vessels during insulitis in nonobese diabetic mice and are involved in lymphoid cell binding to islet endothelium","volume":"92","author":"Hanninen","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.2337\/diacare.46.10.1542","article-title":"Involvement of beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the development of diabetes in obese diabetic mice","volume":"46","author":"Yang","year":"1997","journal-title":"Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.4049\/jimmunol.168.6.2659","article-title":"L-selectin is not required for T cell-mediated autoimmune diabetes","volume":"168","author":"Friedline","year":"2002","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/intimm\/dxh036","article-title":"Role of L-selectin in the development of autoimmune diabetes in non-obese diabetic mice","volume":"16","author":"Mora","year":"2004","journal-title":"Int. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1084\/jem.171.3.801","article-title":"Naive and memory T cells show distinct pathways of lymphocyte recirculation","volume":"171","author":"Mackay","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/366695a0","article-title":"L-selectin-mediated lymphocyte rolling on MAdCAM-1","volume":"366","author":"Berg","year":"1993","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1083\/jcb.114.2.343","article-title":"The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor","volume":"114","author":"Berg","year":"1991","journal-title":"J. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.4049\/jimmunol.163.3.1382","article-title":"Nasal-associated lymphoid tissue: Phenotypic and functional evidence for the primary role of peripheral node addressin in naive lymphocyte adhesion to high endothelial venules in a mucosal site","volume":"163","author":"Csencsits","year":"1999","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1016\/S0002-9440(10)63722-4","article-title":"Detection of a sulfotransferase (HEC-GlcNAc6ST) in high endothelial venules of lymph nodes and in high endothelial venule-like vessels within ectopic lymphoid aggregates: Relationship to the MECA-79 epitope","volume":"164","author":"Bistrup","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S1074-7613(01)00188-1","article-title":"Sulfation of L-selectin ligands by an HEV-restricted sulfotransferase regulates lymphocyte homing to lymph nodes","volume":"15","author":"Hemmerich","year":"2001","journal-title":"Immunity"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/0092-8674(93)90730-E","article-title":"Following a diabetogenic T cell from genesis through pathogenesis","volume":"74","author":"Katz","year":"1993","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1084\/jem.20040139","article-title":"In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes","volume":"199","author":"Tang","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1084\/jem.20040180","article-title":"CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes","volume":"199","author":"Tarbell","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1172\/JCI200420483","article-title":"Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells","volume":"114","author":"Salomon","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1084\/jem.20051409","article-title":"Where CD4+CD25+ T reg cells impinge on autoimmune diabetes","volume":"202","author":"Chen","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1084\/jem.20042398","article-title":"Single cell analysis shows decreasing FoxP3 and TGFbeta1 coexpressing CD4+CD25+ regulatory T cells during autoimmune diabetes","volume":"201","author":"Pop","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00125-003-1089-5","article-title":"The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure","volume":"46","author":"Roep","year":"2003","journal-title":"Diabetologia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.2337\/diab.42.11.1656","article-title":"Endothelial cell-binding properties of lymphocytes infiltrated into human diabetic pancreas. Implications for pathogenesis of IDDM","volume":"42","author":"Hanninen","year":"1993","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00125-004-1613-2","article-title":"Homing of human autoreactive T cells into pancreatic tissue of NOD-scid mice","volume":"48","author":"Kardol","year":"2005","journal-title":"Diabetologia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"583","DOI":"10.2337\/diab.46.4.583","article-title":"Glutamate decarboxylase-reactive peripheral blood lymphocytes from patients with IDDM express gut-specific homing receptor alpha4beta7-integrin","volume":"46","author":"Paronen","year":"1997","journal-title":"Diabetes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.4049\/jimmunol.160.12.6018","article-title":"Mucosal addressin is required for the development of diabetes in nonobese diabetic mice","volume":"160","author":"Hanninen","year":"1998","journal-title":"J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1002\/eji.200324405","article-title":"Diabetogenic T cells are primed both in pancreatic and gut-associated lymph nodes in NOD mice","volume":"33","author":"Jaakkola","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15995","DOI":"10.1073\/pnas.0508122102","article-title":"The role of TNF-alpha in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: Analysis of dendritic cell maturation","volume":"102","author":"Lee","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1084\/jem.20061631","article-title":"Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice","volume":"204","author":"Tarbell","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/nm924","article-title":"TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes","volume":"9","author":"Belghith","year":"2003","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1172\/JCI27191","article-title":"Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs","volume":"116","author":"Bresson","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1172\/JCI28941","article-title":"Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo","volume":"116","author":"Zhang","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S2213-8587(22)00351-5","article-title":"FDA approves teplizumab: A milestone in type 1 diabetes","volume":"11","author":"Hirsch","year":"2023","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1056\/NEJMoa1902226","article-title":"An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes","volume":"381","author":"Herold","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_52","first-page":"118ra112","article-title":"Teplizumab induces human gut-tropic regulatory cells in humanized mice and patients","volume":"4","author":"Henegariu","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e91709","DOI":"10.1172\/jci.insight.91709","article-title":"Microbiota control immune regulation in humanized mice","volume":"2","author":"Vudattu","year":"2017","journal-title":"JCI Insight"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.humimm.2008.08.290","article-title":"Generation and function of human regulatory CD8+ T cells induced by a humanized OKT3 monoclonal antibody hOKT3gamma1 (Ala-Ala)","volume":"69","author":"Ablamunits","year":"2008","journal-title":"Hum. Immunol."},{"doi-asserted-by":"crossref","unstructured":"Chitnis, T., Kaskow, B.J., Case, J., Hanus, K., Li, Z., Varghese, J.F., Healy, B.C., Gauthier, C., Saraceno, T.J., and Saxena, S. (2022). Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects. Front. Immunol., 13.","key":"ref_55","DOI":"10.3389\/fimmu.2022.956907"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1002\/eji.201040485","article-title":"Acquisition of regulatory function by human CD8(+) T cells treated with anti-CD3 antibody requires TNF","volume":"40","author":"Ablamunits","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1089\/scd.2014.0551","article-title":"Evidence that \u03b27 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1","volume":"25","author":"Murakami","year":"2016","journal-title":"Stem Cells Dev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1093\/ecco-jcc\/jjad199","article-title":"Efficacy and Safety of the Anti-mucosal Addressin Cell Adhesion Molecule-1 Antibody Ontamalimab in Patients with Moderate-to-Severe Ulcerative Colitis or Crohn\u2019s Disease","volume":"18","author":"Vermeire","year":"2024","journal-title":"J. Crohns Colitis"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/ecco-jcc\/jjab023","article-title":"Long-term Safety and Efficacy of the Anti-MAdCAM-1 Monoclonal Antibody Ontamalimab [SHP647] for the Treatment of Ulcerative Colitis: The Open-label Study TURANDOT II","volume":"15","author":"Reinisch","year":"2021","journal-title":"J. Crohns Colitis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1093\/ibd\/izab215","article-title":"Long-Term Safety and Efficacy of the Anti-Mucosal Addressin Cell Adhesion Molecule-1 Monoclonal Antibody Ontamalimab (SHP647) for the Treatment of Crohn\u2019s Disease: The OPERA II Study","volume":"28","author":"Reinisch","year":"2022","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1136\/gutjnl-2016-313457","article-title":"Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn\u2019s disease: Report of the OPERA study","volume":"67","author":"Sandborn","year":"2018","journal-title":"Gut"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/bph.13654","article-title":"Physiologically relevant binding affinity quantification of monoclonal antibody PF-00547659 to mucosal addressin cell adhesion molecule for in vitro in vivo correlation","volume":"174","author":"Wang","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0002-9440(10)61738-5","article-title":"Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1\/alpha4beta1 integrin, peripheral node addressin\/L-selectin, and lymphocyte function-associated antigen-1 adhesion pathways","volume":"159","author":"Xu","year":"2001","journal-title":"Am. J. Pathol."},{"doi-asserted-by":"crossref","unstructured":"Guo, J., Xu, Z., Gunderson, R.C., Xu, B., and Michie, S.A. (2023). LFA-1\/ICAM-1 Adhesion Pathway Mediates the Homeostatic Migration of Lymphocytes from Peripheral Tissues into Lymph Nodes through Lymphatic Vessels. Biomolecules, 13.","key":"ref_64","DOI":"10.3390\/biom13081194"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11350\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:17:41Z","timestamp":1760113061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/21\/11350"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":64,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252111350"],"URL":"https:\/\/doi.org\/10.3390\/ijms252111350","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,10,22]]}}}