MAP4K4 negatively regulates CD8 T cell-mediated antitumor and antiviral immunity.


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
27 03 2020
Historique:
received: 30 05 2019
revised: 01 11 2019
accepted: 27 02 2020
entrez: 30 3 2020
pubmed: 30 3 2020
medline: 1 1 2021
Statut: ppublish

Résumé

During cytotoxic T cell activation, lymphocyte function-associated antigen-1 (LFA-1) engages its ligands on antigen-presenting cells (APCs) or target cells to enhance T cell priming or lytic activity. Inhibiting LFA-1 dampens T cell-dependent symptoms in inflammation, autoimmune diseases, and graft-versus-host disease. However, the therapeutic potential of augmenting LFA-1 function is less explored. Here, we show that genetic deletion or inhibition of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) enhances LFA-1 activation on CD8 T cells and improves their adherence to APCs or LFA-1 ligand. In addition, loss of

Identifiants

pubmed: 32220977
pii: 5/45/eaay2245
doi: 10.1126/sciimmunol.aay2245
pii:
doi:

Substances chimiques

Intracellular Signaling Peptides and Proteins 0
Lymphocyte Function-Associated Antigen-1 0
MAP4K4 protein, human EC 2.7.1.11
Protein Serine-Threonine Kinases EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Auteurs

Emel Esen (E)

Department of Molecular Oncology, Genentech, South San Francisco, CA, USA.

Ismail Sergin (I)

Department of Molecular Oncology, Genentech, South San Francisco, CA, USA.

Rajiv Jesudason (R)

Department of Molecular Oncology, Genentech, South San Francisco, CA, USA.

Patricia Himmels (P)

Department of Molecular Oncology, Genentech, South San Francisco, CA, USA.

Joshua D Webster (JD)

Department of Research Pathology, Genentech, South San Francisco, CA, USA.

Hua Zhang (H)

Department of Translational Immunology, Genentech, South San Francisco, CA, USA.

Min Xu (M)

Department of Translational Immunology, Genentech, South San Francisco, CA, USA.

Robert Piskol (R)

Department of Bioinformatics, Genentech, South San Francisco, CA, USA.

Erin McNamara (E)

Department of Translational Oncology, Genentech, South San Francisco, CA, USA.

Stephen Gould (S)

Department of Translational Oncology, Genentech, South San Francisco, CA, USA.

Aude-Hélène Capietto (AH)

Department of Cancer Immunology, Genentech, South San Francisco, CA, USA.

Lélia Delamarre (L)

Department of Cancer Immunology, Genentech, South San Francisco, CA, USA.

Kevin Walsh (K)

Department of Molecular Oncology, Genentech, South San Francisco, CA, USA. walsh.kevin@gene.com ye.weilan@gene.com.

Weilan Ye (W)

Department of Molecular Oncology, Genentech, South San Francisco, CA, USA. walsh.kevin@gene.com ye.weilan@gene.com.

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Classifications MeSH