PMID- 31262842
OWN - NLM
STAT- MEDLINE
DCOM- 20200610
LR  - 20200610
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 216
IP  - 9
DP  - 2019 Sep 2
TI  - Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in 
      dendritic cells.
PG  - 2091-2112
LID - 10.1084/jem.20190041 [doi]
AB  - Conventional type 1 dendritic cells (cDC1s) are inherently resistant to many 
      viruses but, paradoxically, possess fewer acidic phagosomes that enable antigen 
      retention and cross-presentation. We report that palmitoyl-protein thioesterase 1 
      (PPT1), which catabolizes lipid-modified proteins in neurons, is highly expressed 
      in cDC1s. PPT1-deficient DCs are more susceptible to vesicular stomatitis virus 
      (VSV) infection, and mice with PPT1 deficiency in cDC1s show impaired response to 
      VSV. Conversely, PPT1-deficient cDC1s enhance the priming of naive CD8(+) T cells 
      into tissue-resident KLRG1(+) effectors and memory T cells, resulting in rapid 
      clearance of tumors and Listeria monocytogenes Mechanistically, PPT1 protects 
      steady state DCs from viruses by promoting antigen degradation and endosomal 
      acidification via V-ATPase recruitment. After DC activation, immediate 
      down-regulation of PPT1 is likely to facilitate efficient cross-presentation, 
      production of costimulatory molecules and inflammatory cytokines. Thus, PPT1 acts 
      as a molecular rheostat that allows cDC1s to crossprime efficiently without 
      compromising viral resistance. These results suggest potential therapeutics to 
      enhance cDC1-dependent crosspriming.
CI  - (c) 2019 Ou et al.
FAU - Ou, Pengju
AU  - Ou P
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
AD  - Department of Chemotherapy, First Affiliated Hospital of Fujian Medical 
      University, Fuzhou, Fujian, China.
FAU - Wen, Lifen
AU  - Wen L
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
FAU - Liu, Xiaoli
AU  - Liu X
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
FAU - Huang, Jiancheng
AU  - Huang J
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
FAU - Huang, Xiaoling
AU  - Huang X
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
FAU - Su, Chaofei
AU  - Su C
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
FAU - Wang, Ling
AU  - Wang L
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
FAU - Ni, Hai
AU  - Ni H
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China.
FAU - Reizis, Boris
AU  - Reizis B
AUID- ORCID: 0000-0003-1140-7853
AD  - Department of Pathology, New York University School of Medicine, New York, NY.
FAU - Yang, Cliff Y
AU  - Yang CY
AUID- ORCID: 0000-0002-2162-2912
AD  - Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, 
      Guangzhou, Guangdong, China yangkeli6@mail.sysu.edu.cn.
AD  - Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of 
      Education, Guangzhou, Guangdong, China.
LA  - eng
GR  - R01 AI072571/AI/NIAID NIH HHS/United States
GR  - R37 AI072571/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190701
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Acids)
RN  - 0 (Antigens)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
RN  - EC 3.1.2.22 (palmitoyl-protein thioesterase)
SB  - IM
MH  - Acids/metabolism
MH  - Animals
MH  - Antigens/immunology
MH  - Cross-Priming/*immunology
MH  - Dendritic Cells/*immunology
MH  - *Disease Resistance
MH  - Immunity
MH  - Listeria monocytogenes
MH  - Mice, Knockout
MH  - Phagosomes/metabolism
MH  - T-Lymphocytes/*immunology
MH  - Thiolester Hydrolases/*metabolism
MH  - Vesicular Stomatitis/*immunology/*virology
MH  - Vesiculovirus/*immunology
PMC - PMC6719428
EDAT- 2019/07/03 06:00
MHDA- 2020/06/11 06:00
PMCR- 2020/03/02
CRDT- 2019/07/03 06:00
PHST- 2019/01/09 00:00 [received]
PHST- 2019/05/05 00:00 [revised]
PHST- 2019/06/12 00:00 [accepted]
PHST- 2019/07/03 06:00 [pubmed]
PHST- 2020/06/11 06:00 [medline]
PHST- 2019/07/03 06:00 [entrez]
PHST- 2020/03/02 00:00 [pmc-release]
AID - jem.20190041 [pii]
AID - 20190041 [pii]
AID - 10.1084/jem.20190041 [doi]
PST - ppublish
SO  - J Exp Med. 2019 Sep 2;216(9):2091-2112. doi: 10.1084/jem.20190041. Epub 2019 Jul 
      1.