| First Author | Verjans E | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 3 | Pages | 1316-23 |
| PubMed ID | 23785120 | Mgi Jnum | J:205444 |
| Mgi Id | MGI:5544875 | Doi | 10.4049/jimmunol.1203147 |
| Citation | Verjans E, et al. (2013) Overexpression of CREMalpha in T cells aggravates lipopolysaccharide-induced acute lung injury. J Immunol 191(3):1316-23 |
| abstractText | Transcription factor cAMP response element modulator (CREM)alpha 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 CREMalpha is upregulated in LPS-induced ALI. During the early phase of ALI (day 1), T cell-specific CREMalpha overexpression enhances the numbers of T cells and expression of TNF-alpha in bronchoalveolar lavage fluid and deteriorates lung functions. On day 3 of ALI, CREMalpha transgenic mice present a stronger inflammatory response with higher levels of TNF-alpha, 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 CREMalpha transgenic mice. Finally, an adoptive transfer of CREM(-/-) CD4(+) T cells, but not of wild-type T cells into RAG-1(-/-) mice results in ameliorated disease levels. Thus, levels of CREM in T cells determine the outcome of ALI, and CREMalpha 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 CREMalpha and an increased susceptibility toward infectious complications, our finding is of potential clinical significance and may enable new therapeutic strategies. |
