{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:11:48Z","timestamp":1761675108315},"reference-count":59,"publisher":"Wiley","issue":"1-2","license":[{"start":{"date-parts":[[2004,7,5]],"date-time":"2004-07-05T00:00:00Z","timestamp":1088985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Scand J Immunol"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Integrins of the very late antigen (VLA) family mediate leucocyte traffic to lymphoid organs under physiological conditions and in chronic inflammatory situations such as autoimmunity. Accordingly, the current thinking is of a positive correlation between VLA expression and capability of the generation of autoimmunity. Herein we discuss recent findings on the defective expression of integrin\u2010type fibronectin receptors \u03b14\u03b21 (VLA\u20104) and \u03b15\u03b21 (VLA\u20105) in the non\u2010obese diabetic (NOD) mouse, a murine model of autoimmune insulin\u2010dependent diabetes mellitus. As compared with normal animals, NOD thymocytes (including the CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup> regulatory T cells) exhibit a decrease in the membrane expression of \u03b15\u03b21, resulting in a functional impairment of fibronectin\u2010mediated interactions, including cell migration. Interestingly, thymocytes that are trapped within the giant perivascular spaces seen in NOD thymus are consistently \u03b15\u03b21 negative, suggesting that the progressive arrest of mature cells can be related to the \u03b15\u03b21 defect. Peripheral T cells also exhibit decreased \u03b15\u03b21 membrane expression and impaired fibronectin\u2010driven migration. Additionally, we observed a defect in \u03b14\u03b21 fibronectin receptor expression in NOD macrophages. Peritoneal, bone marrow\u2010derived\u2010precursor, as well as thymic macrophages of NOD mice showed an impaired upregulation of \u03b14\u2010integrin chain expression, dependent on the level of macrophage maturation. Overall these data lead to the notion that NOD leucocytes bear distinct fibronectin receptor\u2010mediated cell migration defects, which may be involved in the pathogenesis and\/or pathophysiology of the autoimmune events seen in NOD mice. Further studies will be helpful to define whether or not this concept can be applied for other autoimmune diseases.<\/jats:p>","DOI":"10.1111\/j.0300-9475.2004.01465.x","type":"journal-article","created":{"date-parts":[[2004,7,5]],"date-time":"2004-07-05T19:20:35Z","timestamp":1089055235000},"page":"30-38","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fibronectin Receptor Defects in NOD Mouse Leucocytes: Possible Consequences for Type 1 Diabetes"],"prefix":"10.1111","volume":"60","author":[{"given":"S. B.","family":"Geutskens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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