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We explored whether similar changes in CD44 activity are seen <jats:italic>in vivo<\/jats:italic> using murine alopecia areata (AA) as a chronic, organ\u2010related autoimmune disease model system. Expression of the activated, hyaluronan\u2010binding form of CD44, and of CD49d, was elevated in draining lymph node cells (LNC) of AA\u2010affected mice as compared to control mice. LNC of AA mice displayed increased motility, proliferative activity and apoptosis resistance, which were equally well inhibited by anti\u2010CD44 and anti\u2010CD49d. The latter is the sequelae of the association between CD44 and CD49d that is seen in activated lymphocytes. Significantly, due to CD44\u2010CD49d complex formation, CD44 gains access to focal adhesion kinase and CD49d gains access to CD44\u2010associated lck and ezrin, such that downstream kinases become activated <jats:italic>via<\/jats:italic> CD44 or CD49d engagement. Thus, by their association, CD44 and CD49d mutually avail themselves of the partner's signaling pathways and the ligand binding of each one triggers signaling pathways of both. This strongly influences the lymphocytes\u2019 activation state and function.<\/jats:p>","DOI":"10.1002\/eji.200636158","type":"journal-article","created":{"date-parts":[[2006,10,14]],"date-time":"2006-10-14T00:21:17Z","timestamp":1160785277000},"page":"3017-3032","source":"Crossref","is-referenced-by-count":28,"title":["<i>In vivo <\/i>CD44\u2010CD49d complex formation in autoimmune disease has consequences on T cell activation and apoptosis resistance"],"prefix":"10.1002","volume":"36","author":[{"given":"Rachid","family":"Marhaba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Freyschmidt\u2010Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Z\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,10,30]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:HIJO.0000032354.94213.69"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1004"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90694-A"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0134(20000501)39:2<103::AID-PROT1>3.0.CO;2-G"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.1.257"},{"key":"e_1_2_7_6_2","doi-asserted-by":"crossref","first-page":"27641","DOI":"10.1074\/jbc.M003084200","article-title":"Differences in hyaluronic acid mediated functions and signaling in arterial, microvessel, and vein\u2010derived human endothelial cells.","volume":"275","author":"Lokeshwar V. 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