Autophagy Gene Atg16l1 Prevents Lethal T Cell Alloreactivity Mediated by Dendritic Cells

被引：114

作者：

Hubbard-Lucey, Vanessa M. ^{[1
,2
]}

Shono, Yusuke ^{[3
]}

Maurer, Katie ^{[1
,4
]}

West, Mallory L. ^{[3
]}

Singer, Natalie V. ^{[3
]}

Ziegler, Carly G. K. ^{[5
]}

Lezcano, Cecilia ^{[6
]}

Motta, Ana Carolina Fragoso ^{[6
]}

Schmid, Karin ^{[7
]}

Levi, Samuel M. ^{[8
]}

Murphy, George F. ^{[6
]}

Liu, Chen ^{[9
]}

Winkler, Jeffrey D. ^{[8
,10
]}

Amaravadi, Ravi K. ^{[10
,11
]}

Rogler, Gerhard ^{[12
]}

Dickinson, Anne M. ^{[13
]}

Holler, Ernst ^{[7
]}

van den Brink, Marcel R. M. ^{[3
,14
]}

Cadwell, Ken ^{[1
,2
]}

机构：

[1] Skirball Inst, Kimmel Ctr Biol & Med, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

[3] Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10065 USA

[4] NYU, Sch Med, Sackler Inst Grad Biomed Sci, New York, NY 10016 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Computat Biol & Immunol, New York, NY 10065 USA

[6] Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Dermatopathol, Boston, MA 02115 USA

[7] Univ Regensburg, Univ Med Ctr, Dept Haematol & Oncol, D-93053 Regensburg, Germany

[8] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA

[9] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA

[10] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[11] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[12] Univ Zurich Hosp, Dept Gastroenterol, CH-8006 Zurich, Switzerland

[13] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[14] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

来源：

IMMUNITY | 2014年 / 41卷 / 04期

关键词：

VERSUS-HOST-DISEASE; TRANSMEMBRANE; 5; STEM-CELL; PROTEIN; EXPRESSION; DEGRADATION; LAPTM5; TRANSPLANTATION; MECHANISMS; PHAGOSOMES;

D O I：

10.1016/j.immuni.2014.09.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：579 / 591

页数：13

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