| First Author | Ou P | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 9 | Pages | 2091-2112 |
| PubMed ID | 31262842 | Mgi Jnum | J:301929 |
| Mgi Id | MGI:6364413 | Doi | 10.1084/jem.20190041 |
| Citation | Ou P, et al. (2019) Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells. J Exp Med 216(9):2091-2112 |
| abstractText | 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. |
