• Eva Verjans, Kim Ohl, Yin Yu, Ralph Lippe, Angela Schippers, Anastasia Wiener, Johannes Roth, Norbert Wagner, Stefan Uhlig, Klaus Tenbrock, and Christian Martin.
• Department of Pediatrics, Medical Faculty, Rheinisch-Westfaelische Technische Hochschule Aachen University, 52074 Aachen, Germany.
• J. Immunol. 2013 Aug 1;191(3):1316-23.

AbstractTranscription factor cAMP response element modulator (CREM)α 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 CREMα is upregulated in LPS-induced ALI. During the early phase of ALI (day 1), T cell-specific CREMα overexpression enhances the numbers of T cells and expression of TNF-α in bronchoalveolar lavage fluid and deteriorates lung functions. On day 3 of ALI, CREMα transgenic mice present a stronger inflammatory response with higher levels of TNF-α, 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 CREMα 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 CREMα 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 CREMα and an increased susceptibility toward infectious complications, our finding is of potential clinical significance and may enable new therapeutic strategies.

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