PMID- 25817470
OWN - NLM
STAT- MEDLINE
DCOM- 20150824
LR  - 20181113
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 181
IP  - 1
DP  - 2015 Jul
TI  - Interleukin-2 treatment reverses effects of cAMP-responsive element modulator 
      alpha-over-expressing T cells in autoimmune-prone mice.
PG  - 76-86
LID - 10.1111/cei.12629 [doi]
AB  - 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 (T(reg)) and effector T cells in the 
      periphery. Previously, we identified the cAMP-responsive element modulator alpha 
      (CREMalpha) 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 CREMalpha in T cells (CD2CREMalphatg), we provided in-vivo evidence that 
      CREMalpha indeed suppresses IL-2 production. To analyse the effects of CREMalpha in an 
      autoimmune prone mouse model we introduced a Fas mutation in the CD2CREMalphatg mice 
      (FVB/Fas(-/-) CD2CREMalphatg). Overexpression of CREMalpha 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)-gamma-producing T cells and reduced percentages of T(regs). 
      Treatment of FVB/Fas(-/-) CD2CREMalphatg mice with IL-2 restored the percentage of 
      T(regs) and reversed increased IFN-gamma production, but did not affect the number of 
      DNTs. Our data indicate that CREMalpha 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.
CI  - (c) 2015 British Society for Immunology.
FAU - Ohl, K
AU  - Ohl K
AD  - Department of Pediatrics, RWTH Aachen, Aachen, Germany.
AD  - IZKF Aachen, Medical Faculty, RWTH Aachen, Aachen, Germany.
FAU - Wiener, A
AU  - Wiener A
AD  - Department of Pediatrics, RWTH Aachen, Aachen, Germany.
FAU - Schippers, A
AU  - Schippers A
AD  - Department of Pediatrics, RWTH Aachen, Aachen, Germany.
FAU - Wagner, N
AU  - Wagner N
AD  - Department of Pediatrics, RWTH Aachen, Aachen, Germany.
FAU - Tenbrock, K
AU  - Tenbrock K
AD  - Department of Pediatrics, RWTH Aachen, Aachen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150514
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Fas protein, mouse)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-2)
RN  - 0 (fas Receptor)
RN  - 135844-64-3 (Cyclic AMP Response Element Modulator)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*cytology/immunology
MH  - Cyclic AMP Response Element Modulator/*biosynthesis/genetics
MH  - Immunoglobulin G/blood/immunology
MH  - Interferon-gamma/biosynthesis
MH  - Interleukin-2/biosynthesis/*pharmacology
MH  - Lupus Erythematosus, Systemic/genetics/*immunology
MH  - Lymphatic Diseases/genetics/immunology
MH  - Lymphocyte Count
MH  - Mice
MH  - Mice, Knockout
MH  - Splenomegaly/genetics/immunology
MH  - T-Lymphocytes, Regulatory/*cytology/immunology
MH  - fas Receptor/genetics
PMC - PMC4469157
OTO - NOTNLM
OT  - CREM
OT  - IL-2
OT  - SLE
OT  - regulatory T cells
EDAT- 2015/03/31 06:00
MHDA- 2015/08/25 06:00
PMCR- 2016/07/01
CRDT- 2015/03/31 06:00
PHST- 2015/03/09 00:00 [accepted]
PHST- 2015/03/31 06:00 [entrez]
PHST- 2015/03/31 06:00 [pubmed]
PHST- 2015/08/25 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - 10.1111/cei.12629 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2015 Jul;181(1):76-86. doi: 10.1111/cei.12629. Epub 2015 May 
      14.