Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.
Immunity
; 41(4): 579-91, 2014 Oct 16.
Article
in En
| MEDLINE
| ID: mdl-25308334
ABSTRACT
Atg16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with inflammatory bowel disease. Here we find that Atg16L1 deficiency leads to an exacerbated graft-versus-host disease (GVHD) in a mouse model of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Atg16L1-deficient allo-HSCT recipients with GVHD displayed increased T cell proliferation due to increased dendritic cell (DC) numbers and costimulatory molecule expression. Reduced autophagy within DCs was associated with lysosomal abnormalities and decreased amounts of A20, a negative regulator of DC activation. These results broaden the function of Atg16L1 and the autophagy pathway to include a role in limiting a DC-mediated response during inflammatory disease, such as GVHD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dendritic Cells
/
CD4-Positive T-Lymphocytes
/
Carrier Proteins
/
CD8-Positive T-Lymphocytes
/
Graft vs Host Disease
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2014
Type:
Article
Affiliation country:
United States