{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:02:21Z","timestamp":1779890541898,"version":"3.53.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Transcription factor cAMP response element modulator (CREM)\u03b1 contributes to various cellular and molecular abnormalities in T cells, including increased IL-17 and decreased IL-2 expression. For development of acute lung injury (ALI), the invasion and regulation of immune cells are highly important, but the role of T cells remains unclear. In this study, we show that CREM\u03b1 is upregulated in LPS-induced ALI. During the early phase of ALI (day 1), T cell\u2013specific CREM\u03b1 overexpression enhances the numbers of T cells and expression of TNF-\u03b1 in bronchoalveolar lavage fluid and deteriorates lung functions. On day 3 of ALI, CREM\u03b1 transgenic mice present a stronger inflammatory response with higher levels of TNF-\u03b1, IL-6, and IL-17 correlating with increased numbers of T cells and neutrophils in bronchoalveolar lavage fluid, whereas expression of Foxp3 and IL-2 and numbers of regulatory T cells are decreased. These changes result in restricted lung function in CREM\u03b1 transgenic mice. Finally, an adoptive transfer of CREM\u2212\/\u2212 CD4+ T cells, but not of wild-type T cells into RAG-1\u2212\/\u2212 mice results in ameliorated disease levels. Thus, levels of CREM in T cells determine the outcome of ALI, and CREM\u03b1 transgenic animals represent a model in which proinflammatory T cells aggravate ALI in different phases of the disease. Given the fact that patients with autoimmune diseases like systemic lupus erythematosus show higher levels of CREM\u03b1 and an increased susceptibility toward infectious complications, our finding is of potential clinical significance and may enable new therapeutic strategies.<\/jats:p>","DOI":"10.4049\/jimmunol.1203147","type":"journal-article","created":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T04:36:02Z","timestamp":1371702962000},"page":"1316-1323","source":"Crossref","is-referenced-by-count":21,"title":["Overexpression of CREM\u03b1 in T Cells Aggravates Lipopolysaccharide-Induced Acute Lung Injury"],"prefix":"10.1093","volume":"191","author":[{"given":"Eva","family":"Verjans","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]},{"name":"Institute of Pharmacology and Toxicology, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Ohl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Lippe","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University of Muenster , 48149 Muenster,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Schippers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Wiener","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roth","sequence":"additional","affiliation":[{"name":"Institute of Immunology, University of Muenster , 48149 Muenster,","place":["Germany"]},{"name":"Interdisciplinary Center for Clinical Research, University of Muenster , 48149 Muenster,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Uhlig","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Tenbrock","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rheinisch-Westfaelische Technische Hochschule Aachen University , 52074 Aachen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"key":"2025032405122829600_r1","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMoa050333","article-title":"Incidence and outcomes of acute lung injury","volume":"353","author":"Rubenfeld","year":"2005","journal-title":"N. 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