PMID- 25077962
OWN - NLM
STAT- MEDLINE
DCOM- 20150202
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 289
IP  - 38
DP  - 2014 Sep 19
TI  - Deficiency of autophagy in dendritic cells protects against experimental 
      autoimmune encephalomyelitis.
PG  - 26525-26532
LID - S0021-9258(20)48479-0 [pii]
LID - 10.1074/jbc.M114.575860 [doi]
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) in the 
      immune system. DCs present antigens to CD8 and CD4 T cells in the context of 
      class I or II MHC. Recent evidence suggests that autophagy, a conserved 
      intracellular degradation pathway, regulates class II antigen presentation. In 
      vitro studies have shown that deletion of autophagy-related genes reduced antigen 
      presentation by APCs to CD4 T cells. In vivo studies confirmed these findings in 
      the context of infectious diseases. However, the relevance of autophagy-mediated 
      antigen presentation in autoimmunity remains to be elucidated. Here, we report 
      that loss of autophagy-related gene 7 (Atg7) in DCs ameliorated experimental 
      autoimmune encephalomyelitis (EAE), a CD4 T cell-mediated mouse model of multiple 
      sclerosis, by reducing in vivo priming of T cells. In contrast, severity of 
      hapten-induced contact hypersensitivity, in which CD8 T cells and NK cells play 
      major roles, was unaffected. Administration of the autophagy-lysosomal inhibitor 
      chloroquine, before EAE onset, delayed disease progression and, when administered 
      after the onset, reduced disease severity. Our data show that autophagy is 
      required in DCs for induction of EAE and suggest that autophagy might be a 
      potential target for treating CD4 T cell-mediated autoimmune conditions.
CI  - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Bhattacharya, Abhisek
AU  - Bhattacharya A
AD  - Departments of Medicine and Baylor College of Medicine, Houston, Texas 77030; 
      Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Parillon, Xyanthine
AU  - Parillon X
AD  - Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Zeng, Shenyan
AU  - Zeng S
AD  - Departments of Medicine and Baylor College of Medicine, Houston, Texas 77030.
FAU - Han, Shuhua
AU  - Han S
AD  - Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 
      77030.
FAU - Eissa, N Tony
AU  - Eissa NT
AD  - Departments of Medicine and Baylor College of Medicine, Houston, Texas 77030; 
      Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas 
      77030. Electronic address: teissa@bcm.edu.
LA  - eng
GR  - R01 HL69033/HL/NHLBI NIH HHS/United States
GR  - CA125123/CA/NCI NIH HHS/United States
GR  - AI036211/AI/NIAID NIH HHS/United States
GR  - R01 HL069033/HL/NHLBI NIH HHS/United States
GR  - P30 CA125123/CA/NCI NIH HHS/United States
GR  - P30 AI036211/AI/NIAID NIH HHS/United States
GR  - S10 RR024574/RR/NCRR NIH HHS/United States
GR  - RR024574/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140730
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Atg7 protein, mouse)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 6.2.1.45 (Autophagy-Related Protein 7)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - *Autophagy/drug effects
MH  - Autophagy-Related Protein 7
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Chloroquine/pharmacology/therapeutic use
MH  - Dendritic Cells/*physiology
MH  - Drug Evaluation, Preclinical
MH  - Encephalomyelitis, Autoimmune, Experimental/drug therapy/*immunology/pathology
MH  - Lysosomes/drug effects/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microtubule-Associated Proteins/*genetics/metabolism
MH  - Spleen/immunology/pathology
MH  - Thymus Gland/immunology/pathology
PMC - PMC4176242
OTO - NOTNLM
OT  - Antigen Presentation
OT  - Autoimmunity
OT  - Autophagy
OT  - Autophagy-related Protein 7 (ATG7)
OT  - Dendritic Cell
OT  - Multiple Sclerosis
EDAT- 2014/08/01 06:00
MHDA- 2015/02/03 06:00
PMCR- 2015/09/19
CRDT- 2014/08/01 06:00
PHST- 2014/08/01 06:00 [entrez]
PHST- 2014/08/01 06:00 [pubmed]
PHST- 2015/02/03 06:00 [medline]
PHST- 2015/09/19 00:00 [pmc-release]
AID - S0021-9258(20)48479-0 [pii]
AID - M114.575860 [pii]
AID - 10.1074/jbc.M114.575860 [doi]
PST - ppublish
SO  - J Biol Chem. 2014 Sep 19;289(38):26525-26532. doi: 10.1074/jbc.M114.575860. Epub 
      2014 Jul 30.