[PDF][PDF] Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells

VM Hubbard-Lucey, Y Shono, K Maurer, ML West… - Immunity, 2014 - cell.com
VM Hubbard-Lucey, Y Shono, K Maurer, ML West, NV Singer, CGK Ziegler, C Lezcano…
Immunity, 2014cell.com
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 …
Summary
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.
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