1. Autophagy Gene Atg16l1 Prevents Lethal T Cell Alloreactivity Mediated by Dendritic Cells.
- Author
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Hubbard-Lucey, Vanessa M., Shono, Yusuke, Maurer, Katie, West, Mallory L., Singer, Natalie V., Ziegler, Carly G.K., Lezcano, Cecilia, Motta, Ana Carolina Fragoso, Schmid, Karin, Levi, Samuel M., Murphy, George F., Liu, Chen, Winkler, Jeffrey D., Amaravadi, Ravi K., Rogler, Gerhard, Dickinson, Anne M., Holler, Ernst, van den Brink, Marcel R.M., and Cadwell, Ken
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AUTOPHAGY , *DENDRITIC cells , *INFLAMMATORY bowel diseases , *T cells , *GRAFT versus host disease , *HEMATOPOIETIC stem cells , *GENE expression , *GENETICS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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