PMID- 25979422
OWN - NLM
STAT- MEDLINE
DCOM- 20150730
LR  - 20220318
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 42
IP  - 5
DP  - 2015 May 19
TI  - The Autoimmunity-Associated Gene CLEC16A Modulates Thymic Epithelial Cell 
      Autophagy and Alters T Cell Selection.
PG  - 942-52
LID - S1074-7613(15)00171-5 [pii]
LID - 10.1016/j.immuni.2015.04.011 [doi]
AB  - CLEC16A variation has been associated with multiple immune-mediated diseases, 
      including type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, 
      celiac disease, Crohn's disease, Addison's disease, primary biliary cirrhosis, 
      rheumatoid arthritis, juvenile idiopathic arthritis, and alopecia areata. Despite 
      strong genetic evidence implicating CLEC16A in autoimmunity, this gene's broad 
      association with disease remains unexplained. We generated Clec16a knock-down 
      (KD) mice in the nonobese diabetic (NOD) model for type 1 diabetes and found that 
      Clec16a silencing protected against autoimmunity. Disease protection was 
      attributable to T cell hyporeactivity, which was secondary to changes in thymic 
      epithelial cell (TEC) stimuli that drive thymocyte selection. Our data indicate 
      that T cell selection and reactivity were impacted by Clec16a variation in thymic 
      epithelium owing to Clec16a's role in TEC autophagy. These findings provide a 
      functional link between human CLEC16A variation and the immune dysregulation that 
      underlies the risk of autoimmunity.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Schuster, Cornelia
AU  - Schuster C
AD  - Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA, 
      02215, USA.
FAU - Gerold, Kay D
AU  - Gerold KD
AD  - Rudolf Virchow Center/DFG Research Center for Experimental Biomedicine, 
      University of Wurzburg, Josef-Schneider Strasse 2, 97080 Wurzburg, Germany.
FAU - Schober, Kilian
AU  - Schober K
AD  - Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA, 
      02215, USA.
FAU - Probst, Lilli
AU  - Probst L
AD  - Rudolf Virchow Center/DFG Research Center for Experimental Biomedicine, 
      University of Wurzburg, Josef-Schneider Strasse 2, 97080 Wurzburg, Germany.
FAU - Boerner, Kevin
AU  - Boerner K
AD  - Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA, 
      02215, USA.
FAU - Kim, Mi-Jeong
AU  - Kim MJ
AD  - Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA, 
      02215, USA.
FAU - Ruckdeschel, Anna
AU  - Ruckdeschel A
AD  - Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA, 
      02215, USA.
FAU - Serwold, Thomas
AU  - Serwold T
AD  - Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA, 
      02215, USA.
FAU - Kissler, Stephan
AU  - Kissler S
AD  - Joslin Diabetes Center, Harvard Medical School, 1 Joslin Place, Boston, MA, 
      02215, USA; Rudolf Virchow Center/DFG Research Center for Experimental 
      Biomedicine, University of Wurzburg, Josef-Schneider Strasse 2, 97080 Wurzburg, 
      Germany. Electronic address: stephan.kissler@joslin.harvard.edu.
LA  - eng
GR  - P30 DK036836/DK/NIDDK NIH HHS/United States
GR  - P30DK036836/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150512
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (CLEC16A protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Monosaccharide Transport Proteins)
SB  - IM
MH  - Animals
MH  - Autoimmunity/genetics/*immunology
MH  - Autophagy/immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Type 1/immunology
MH  - Disease Models, Animal
MH  - *Epithelial Cells/cytology/immunology
MH  - Gene Knockdown Techniques
MH  - Immunohistochemistry
MH  - Lectins, C-Type/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Monosaccharide Transport Proteins/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/cytology/*immunology
MH  - Thymocytes/cytology/immunology
MH  - *Thymus Gland/cytology/immunology
PMC - PMC4439257
MID - NIHMS685757
EDAT- 2015/05/17 06:00
MHDA- 2015/08/01 06:00
PMCR- 2016/05/19
CRDT- 2015/05/17 06:00
PHST- 2014/10/23 00:00 [received]
PHST- 2015/01/16 00:00 [revised]
PHST- 2015/03/24 00:00 [accepted]
PHST- 2015/05/17 06:00 [entrez]
PHST- 2015/05/17 06:00 [pubmed]
PHST- 2015/08/01 06:00 [medline]
PHST- 2016/05/19 00:00 [pmc-release]
AID - S1074-7613(15)00171-5 [pii]
AID - 10.1016/j.immuni.2015.04.011 [doi]
PST - ppublish
SO  - Immunity. 2015 May 19;42(5):942-52. doi: 10.1016/j.immuni.2015.04.011. Epub 2015 
      May 12.