FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients.
Cell Death Dis
; 6: e1741, 2015 May 07.
Article
in En
| MEDLINE
| ID: mdl-25950471
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Th1 Cells
/
Fas Ligand Protein
/
Th17 Cells
/
Multiple Sclerosis
Type of study:
Observational_studies
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Journal:
Cell Death Dis
Year:
2015
Type:
Article
Affiliation country:
Italy