{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:44:35Z","timestamp":1753886675711,"version":"3.41.2"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,8,2]],"date-time":"2015-08-02T00:00:00Z","timestamp":1438473600000},"content-version":"vor","delay-in-days":213,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100007921","name":"University of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006544","name":"Israeli Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006544","id-type":"DOI","asserted-by":"crossref"}]},{"name":"David Shainberg Fund"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p>Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1\u2010negative (Thy1<jats:sup>\u2212<\/jats:sup>) myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF) and of bleomycin\u2010treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1\u2010deficiency, in vivo, in bleomycin\u2010injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days), as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM) components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1\u2010deficient mice with Thy1<jats:sup>+<\/jats:sup> lymphocytes and Thy1<jats:sup>\u2212<\/jats:sup> myofibroblasts showed fibrosis similar to wild\u2010type mice and an increased number of CD4\/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.<\/jats:p>","DOI":"10.1155\/2015\/942179","type":"journal-article","created":{"date-parts":[[2015,8,2]],"date-time":"2015-08-02T21:02:15Z","timestamp":1438549335000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bleomycin\u2010Treated Chimeric Thy1\u2010Deficient Mice with Thy1\u2010Deficient Myofibroblasts and Thy\u2010Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response"],"prefix":"10.1155","volume":"2015","author":[{"given":"Pazit Y.","family":"Cohen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raphael","family":"Breuer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Zisman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shulamit B.","family":"Wallach-Dayan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,2]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_1_2","DOI":"10.1378\/chest.100.1.238"},{"doi-asserted-by":"publisher","key":"e_1_2_10_2_2","DOI":"10.1378\/chest.108.2.297"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_2","DOI":"10.1006\/mthe.2000.0251"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_2","DOI":"10.1046\/j.1365-2613.2002.00220.x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_2","DOI":"10.1006\/clin.1994.1144"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_2","DOI":"10.1002\/ar.1092320312"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_2","DOI":"10.1165\/ajrcmb\/1.1.65"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_2","DOI":"10.1165\/ajrcmb.26.6.4547"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_2","DOI":"10.1152\/ajplung.1999.277.1.L218"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_2","DOI":"10.1002\/eji.1830200815"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_2","DOI":"10.1089\/jir.1995.15.63"},{"key":"e_1_2_10_12_2","first-page":"277","article-title":"Expression of TGF-\u03b2 isoforms by Thy-1+ and Thy-1- pulmonary fibroblast subsets: evidence for TGF-\u03b2 as a regulator of IL-1-dependent stimulation of IL-6","volume":"13","author":"Silvera M. 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