Title : Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells - Ou_2019_J.Exp.Med_216_2091 |
Author(s) : Ou P , Wen L , Liu X , Huang J , Huang X , Su C , Wang L , Ni H , Reizis B , Yang CY |
Ref : J Exp Med , 216 :2091 , 2019 |
Abstract :
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. |
PubMedSearch : Ou_2019_J.Exp.Med_216_2091 |
PubMedID: 31262842 |
Gene_locus related to this paper: human-PPT1 , mouse-ppt |
Gene_locus | human-PPT1 mouse-ppt |
Ou P, Wen L, Liu X, Huang J, Huang X, Su C, Wang L, Ni H, Reizis B, Yang CY (2019)
Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells
J Exp Med
216 :2091
Ou P, Wen L, Liu X, Huang J, Huang X, Su C, Wang L, Ni H, Reizis B, Yang CY (2019)
J Exp Med
216 :2091