Interleukin‐2 treatment reverses effects of cAMP‐responsive element modulator α‐over‐expressing T cells in autoimmune‐prone mice. (14th May 2015)

• Record Type: Journal Article
• Authors: Ohl, K.; Wiener, A.; Schippers, A.; Wagner, N.; Tenbrock, K.
• Is Part Of: Clinical and experimental immunology. Volume 181:Number 1(2015:Jul.)
• Page Start: 76
• Page End: 86
• Publication Date: 2015-05-14
• Subjects: CREM -- IL‐2 -- regulatory T cells -- SLE; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12629
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: Systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), are often characterized by a failure of self‐tolerance and result in an uncontrolled activation of B cells and effector T cells. Interleukin (IL)‐2 critically maintains homeostasis of regulatory T cells (Treg ) and effector T cells in the periphery. Previously, we identified the cAMP‐responsive element modulator α (CREMα) as a major factor responsible for decreased IL‐2 production in T cells from SLE patients. Additionally, using a transgenic mouse that specifically over‐expresses CREMα in T cells (CD2CREMαtg), we provided in‐vivo evidence that CREMα indeed suppresses IL‐2 production. To analyse the effects of CREMα in an autoimmune prone mouse model we introduced a Fas mutation in the CD2CREMαtg mice (FVB/Fas –/– CD2CREMαtg). Overexpression of CREMα strongly accelerated the lymphadenopathy and splenomegaly in the FVB/Fas –/– mice. This was accompanied by a massive expansion of double‐negative (DN) T cells, enhanced numbers of interferon (IFN)‐γ‐producing T cells and reduced percentages of Tregs . Treatment of FVB/Fas –/– CD2CREMαtg mice with IL‐2 restored the percentage of Tregs and reversed increased IFN‐γ production, but did not affect the number of DNTs. Our data indicate that CREMα contributes to the failure of tolerance in SLE by favouring effector T cells and decreasing regulatory T cells, partially mediated by repression of IL‐2 in vivo .