title: FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients.
abstract: Functionally distinct T-helper (Th) subsets orchestrate immune responses. Maintenance of homeostasis through the tight control of inflammatory Th cells is crucial to avoid autoimmune inflammation. Activation-Induced Cell Death (AICD) regulates homeostasis of T cells, and it has never been investigated in human Th cells. We generated stable clones of inflammatory Th subsets involved in autoimmune diseases, such as Th1, Th17 and Th1/17 cells, from healthy donors (HD) and multiple sclerosis (MS) patients and we measured AICD. We find that human Th1 cells are sensitive, whereas Th17 and Th1/17 are resistant, to AICD. In particular, Th1 cells express high level of FAS-ligand (FASL), which interacts with FAS and leads to caspases' cleavage and ultimately to cell death. In contrast, low FASL expression in Th17 and Th1/17 cells blunts caspase 8 activation and thus reduces cell death. Interestingly, Th cells obtained from healthy individuals and MS patients behave similarly, suggesting that this mechanism could explain the persistence of inflammatory IL-17-producing cells in autoimmune diseases, such as MS, where their generation is particularly substantial.
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation, Rome, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Cencioni
authors.affiliation: 1] Cell Signaling Unit, Santa Lucia Foundation, Rome, Italy [2] Multiple Sclerosis Centre, Santa Lucia Foundation, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Santini
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ruocco
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Borsellino
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Bardi
authors.affiliation: Department of Biology, University Tor Vergata, Rome, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Grasso
authors.affiliation: Department of Neuroscience, University Tor Vergata, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ruggieri
authors.affiliation: Department of Neuroscience, University Tor Vergata, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gasperini
authors.affiliation: 1] Department of Neuroscience "Lancisi", San Camillo Hospital, Rome, Italy [2] Neuroimmunology and Synaptic Plasticity Unit, Santa Lucia Foundation, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Centonze
authors.affiliation: 1] Cell Signaling Unit, Santa Lucia Foundation, Rome, Italy [2] Multiple Sclerosis Centre, Santa Lucia Foundation, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Barilá
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Battistini
authors.affiliation: Neuroimmunology Unit, Santa Lucia Foundation, Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Volpe
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D016022:Case-Control Studies; D016923:Cell Death / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein