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Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells.
Ou, Pengju; Wen, Lifen; Liu, Xiaoli; Huang, Jiancheng; Huang, Xiaoling; Su, Chaofei; Wang, Ling; Ni, Hai; Reizis, Boris; Yang, Cliff Y.
Afiliação
  • Ou P; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Wen L; Department of Chemotherapy, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
  • Liu X; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Huang J; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Huang X; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Su C; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Wang L; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Ni H; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Reizis B; Department of Immunology, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, Guangdong, China.
  • Yang CY; Department of Pathology, New York University School of Medicine, New York, NY.
J Exp Med ; 216(9): 2091-2112, 2019 09 02.
Article em En | MEDLINE | ID: mdl-31262842
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tioléster Hidrolases / Células Dendríticas / Linfócitos T / Vesiculovirus / Apresentação Cruzada / Estomatite Vesicular / Resistência à Doença Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tioléster Hidrolases / Células Dendríticas / Linfócitos T / Vesiculovirus / Apresentação Cruzada / Estomatite Vesicular / Resistência à Doença Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article