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In this study, we found that ex vivo human effector\/memory but not central\/memory Th17 cells express and use the disco\u00efdin domain receptor 1 (DDR1) to migrate in collagen gels. The tyrosine kinase activity of DDR1 is essential to this process since its blockade with the DDR1 kinase inhibitor 7rh and the DDR1 kinase-dead construct inhibited the migration of human Th17 cells. Our results indicated that the DDR1 kinase activity enhanced Th17 cell migration by activating the MAPK\/ERK pathway. We then examined the role of DDR1 in the inflammatory model of collagen-induced arthritis (CIA). Treatment of CIA mice with the DDR1 kinase inhibitor 7rh led to reduced arthritis severity, synovial inflammation and cartilage destruction. DDR1 expression is higher on T cells isolated from CIA mice than on those from na\u00efve mice, and its blockade inhibited Th17 cell infiltration into the joints, which was associated with the inhibition of IL-17 levels. Along these lines, isolated T cells from 7rh-treated arthritic mice showed a drastic reduction in migration in collagen gels compared to those isolated from control arthritic mice. Further, the 7rh treatment reduced the levels of TNF-\u03b1 and IL-1\u03b2 and increased the levels of IL-10, thus promoting an anti-inflammatory environment. Our findings provide an important role for the DDR1 tyrosine kinase in promoting Th17 cell infiltration into inflammatory tissues, especially in collagen-rich tissues like the joints, and in the development of arthritis.<\/jats:p>","DOI":"10.3390\/ijms27136043","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The DDR1 Tyrosine Kinase Promotes Th17 Cell Migration in Three-Dimensional Collagen and into the Joints During Inflammatory Arthritis"],"prefix":"10.3390","volume":"27","author":[{"given":"Chakib","family":"Hamoudi","sequence":"first","affiliation":[{"name":"Division of Infectious and Immune Diseases, CHU de Quebec-Universit\u00e9 Laval Research Center, CHUL, Quebec, QC G1V 4G2, Canada"},{"name":"ARThrite Research Center, Laval University, Quebec, QC G1V4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Toghi","sequence":"additional","affiliation":[{"name":"Division of Infectious and Immune Diseases, CHU de Quebec-Universit\u00e9 Laval Research Center, CHUL, Quebec, QC G1V 4G2, Canada"},{"name":"ARThrite Research Center, Laval University, Quebec, QC G1V4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7525-6252","authenticated-orcid":false,"given":"Anahita","family":"Lashgari","sequence":"additional","affiliation":[{"name":"Division of Infectious and Immune Diseases, CHU de Quebec-Universit\u00e9 Laval Research Center, CHUL, Quebec, QC G1V 4G2, Canada"},{"name":"ARThrite Research Center, Laval University, Quebec, QC G1V4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-2941","authenticated-orcid":false,"given":"Fawzi","family":"Aoudjit","sequence":"additional","affiliation":[{"name":"Division of Infectious and Immune Diseases, CHU de Quebec-Universit\u00e9 Laval Research Center, CHUL, Quebec, QC G1V 4G2, Canada"},{"name":"ARThrite Research Center, Laval University, Quebec, QC G1V4G2, Canada"},{"name":"Department of Microbiology-Infectiology and Immunology, Faculty of Medicine, Laval University, Quebec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1038\/ni.f.212","article-title":"Interstitial leukocyte migration and immune function","volume":"9","author":"Friedl","year":"2008","journal-title":"Nat. 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