title: Astrocytic Fas ligand expression is required to induce T-cell apoptosis and recovery from experimental autoimmune encephalomyelitis.
abstract: 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-γ, 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.
authors.affiliation: Institute of Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Fahad
authors.initials: F
authors.lastname: Haroon
authors.forename: Saoussen
authors.initials: S
authors.lastname: Karray
authors.lastname: Martina Deckert
authors.forename: Dirk
authors.initials: D
authors.lastname: Schlüter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55)