Autophagy gene atg16l1 prevents lethal T cell alloreactivity mediated by dendritic cells Journal Article

   


Authors: Hubbard-Lucey, V. M.; Shono, Y.; Maurer, K.; West, M. L.; Singer, N. V.; Ziegler, C. G. K.; Lezcano, C.; Motta, A. C. F.; Schmid, K.; Levi, S. M.; Murphy, G. F.; Liu, C.; Winkler, J. D.; Amaravadi, R. K.; Rogler, G.; Dickinson, A.; Holler, E.; van den Brink, M. R. M.; Cadwell, K.
Article Title: Autophagy gene atg16l1 prevents lethal T cell alloreactivity mediated by dendritic cells
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 Tcell 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.
Keywords: signal transduction; controlled study; unclassified drug; nonhuman; lymphocyte proliferation; t lymphocyte; animal cell; mouse; gene; gene expression; dendritic cell; animal experiment; animal model; gene function; lymphocyte activation; cellular immunity; nucleotide sequence; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; cell count; autophagy; disease exacerbation; graft recipient; lethality; regulator protein; lysosome storage disease; alloimmunity; a20 protein; female; article; atg16l1 gene
Journal Title: Immunity
Volume: 41
Issue: 4
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2014-10-16
Start Page: 579
End Page: 591
Language: English
DOI: 10.1016/j.immuni.2014.09.011
PROVIDER: scopus
PMCID: PMC4237219
PUBMED: 25308334
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84908137655&partnerID=40&md5=bf6426de388e8821c00d82d84ccf07eb
Notes: Export Date: 1 December 2014 -- Source: Scopus
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Yusuke Shono
    39 Shono
  3. Natalie Singer
    24 Singer
  4. Mallory Lia West
    24 West
  5. Carly Gail Kean Ziegler
    13 Ziegler
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