PMID- 23011975
OWN - NLM
STAT- MEDLINE
DCOM- 20130408
LR  - 20130116
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 43
IP  - 1
DP  - 2013 Jan
TI  - Astrocytic Fas ligand expression is required to induce T-cell apoptosis and 
      recovery from experimental autoimmune encephalomyelitis.
PG  - 115-24
LID - 10.1002/eji.201242679 [doi]
AB  - In T-cell-mediated autoimmune diseases of the CNS, apoptosis of Fas(+) T cells by 
      FasL contributes to resolution of disease. However, the apoptosis-inducing cell 
      population still remains to be identified. To address the role of astrocytic FasL 
      in the regulation of T-cell apoptosis in experimental autoimmune 
      encephalomyelitis, we immunized C57BL/6 glial fibrillary acid protein (GFAP)-Cre 
      FasL(fl/fl) mice selectively lacking FasL in astrocytes with MOG(35-55) peptide. 
      GFAP-Cre FasL(fl/fl) mice were unable to resolve EAE and suffered from persisting 
      demyelination and paralysis, while FasL(fl/fl) control mice recovered. In 
      contrast to FasL(fl/fl) mice, GFAP-Cre FasL(fl/fl) mice failed to induce 
      apoptosis of Fas(+) activated CD4(+) T cells and to increase numbers of Foxp3(+) 
      Treg cells beyond day 15 post immunization, the time point of maximal clinical 
      disease in control mice. The persistence of activated and GM-CSF-producing CD4(+) 
      T cells in GFAP-Cre FasL(fl/fl) mice also resulted in an increased IL-17, IFN-gamma, 
      TNF, and GM-CSF mRNA expression in the CNS. In vitro, FasL(+) but not FasL(-) 
      astrocytes induced caspase-3 expression and apoptosis of activated T cells. In 
      conclusion, FasL expression of astrocytes plays an important role in the control 
      and elimination of autoimmune T cells from the CNS, thereby determining recovery 
      from EAE.
CI  - (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Wang, Xu
AU  - Wang X
AD  - Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, 
      Magdeburg, Germany.
FAU - Haroon, Fahad
AU  - Haroon F
FAU - Karray, Saoussen
AU  - Karray S
FAU - Martina Deckert
AU  - Martina Deckert
FAU - Schluter, Dirk
AU  - Schluter D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121121
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (Cytokines)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxp3 protein, mouse)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Peptide Fragments)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Astrocytes/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/genetics/*immunology
MH  - Fas Ligand Protein/genetics/*metabolism
MH  - Forkhead Transcription Factors/metabolism
MH  - Glial Fibrillary Acidic Protein/immunology
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Multiple Sclerosis/genetics/*immunology
MH  - Myelin-Oligodendrocyte Glycoprotein/immunology
MH  - Peptide Fragments/immunology
MH  - T-Lymphocytes, Regulatory/*immunology
EDAT- 2012/09/27 06:00
MHDA- 2013/04/09 06:00
CRDT- 2012/09/27 06:00
PHST- 2012/05/14 00:00 [received]
PHST- 2012/08/24 00:00 [revised]
PHST- 2012/09/19 00:00 [accepted]
PHST- 2012/09/27 06:00 [entrez]
PHST- 2012/09/27 06:00 [pubmed]
PHST- 2013/04/09 06:00 [medline]
AID - 10.1002/eji.201242679 [doi]
PST - ppublish
SO  - Eur J Immunol. 2013 Jan;43(1):115-24. doi: 10.1002/eji.201242679. Epub 2012 Nov 
      21.