Verjans, Eva and Ohl, Kim and Reiss, Lucy K. and van Wijk, Femke and Toncheva, Antonaneta A. and Wiener, Anastasia and Yu, Yin and Rieg, Annette D. and Gaertner, Vincent D. and Roth, Johannes and Knol, Edward and Kabesch, Michael and Wagner, Norbert and Uhlig, Stefan and Martin, Christian and Tenbrock, Klaus (2015) The cAMP response element modulator (CREM) regulates T(H)2 mediated inflammation. ONCOTARGET, 6 (36). pp. 38538-38551. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
A characteristic feature of allergic diseases is the appearance of a subset of CD4(+) cells known as T(H)2 cells, which is controlled by transcriptional and epigenetic mechanisms. We aimed to analyze the role of CREM, a known transcriptional activator of T cells, with regard to T(H)2 responses and allergic diseases in men and mice. Here we demonstrate that T cells of asthmatic children and PBMCs of adults with atopy express lower mRNA levels of the transcription factor CREM compared to cells from healthy controls. CREM deficiency in murine T cells results in enhanced T(H)2 effector cytokines in vitro and in vivo and CREM-/- mice demonstrate stronger airway hyperresponsiveness in an OVA-induced asthma model. Mechanistically, both direct CREM binding to the IL-4 and IL-13 promoter as well as a decreased IL-2 dependent STAT5 activation suppress the T(H)2 response. Accordingly, mice selectively overexpressing CREMa in T cells display decreased T(H)2 type cytokines in vivo and in vitro, and are protected in an asthma model. Thus, we provide evidence that CREM is a negative regulator of the T(H)2 response and determines the outcome of allergic asthma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUPPRESSES IL-2 PRODUCTION; T-CELLS; GENE-EXPRESSION; ALLERGIC-ASTHMA; TRANSCRIPTIONAL REGULATION; TH2 DIFFERENTIATION; NEGATIVE REGULATOR; PROMOTER; ALPHA; allergic disease; asthmatic response; T cell dysregulation; transcription factor; T(H)2; Immunology Section; Immunity; Immune response |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 May 2019 11:53 |
| Last Modified: | 06 May 2019 11:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4448 |
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