Mechanical Stiffness Controls Dendritic Cell Metabolism and Function.

Dendritic Cells / immunology Humans Immunity, Innate / immunology Immunotherapy / methods Signal Transduction Vascular Stiffness / immunology
PIEZO1 TAZ danger signals dendritic cells immunometabolism inflammation innate immunity mechanoimmunology mechanosensing tension

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
12 01 2021
Historique:
received: 07 01 2020
revised: 04 11 2020
accepted: 15 12 2020
entrez: 13 1 2021
pubmed: 14 1 2021
medline: 5 1 2022
Statut: ppublish

Résumé

Stiffness in the tissue microenvironment changes in most diseases and immunological conditions, but its direct influence on the immune system is poorly understood. Here, we show that static tension impacts immune cell function, maturation, and metabolism. Bone-marrow-derived and/or splenic dendritic cells (DCs) grown in vitro at physiological resting stiffness have reduced proliferation, activation, and cytokine production compared with cells grown under higher stiffness, mimicking fibro-inflammatory disease. Consistently, DCs grown under higher stiffness show increased activation and flux of major glucose metabolic pathways. In DC models of autoimmune diabetes and tumor immunotherapy, tension primes DCs to elicit an adaptive immune response. Mechanistic workup identifies the Hippo-signaling molecule, TAZ, as well as Ca

Identifiants

DOI: 10.1016/j.celrep.2020.108609 PMID: 33440149
pubmed: 33440149
pii: S2211-1247(20)31598-9
doi: 10.1016/j.celrep.2020.108609
pii:
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

108609

Subventions

Organisme : CIHR
ID : FDN-148385
Pays : Canada

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Mainak Chakraborty (M)

Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON M5G 1L7, Canada.

Kevin Chu (K)

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Annie Shrestha (A)

Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Xavier S Revelo (XS)

Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN 55455, USA.

Xiangyue Zhang (X)

School of Medicine, Department of Pathology, Stanford University, Palo Alto, CA, USA.

Matthew J Gold (MJ)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.

Saad Khan (S)

Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON M5G 1L7, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Megan Lee (M)

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Camille Huang (C)

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Masoud Akbari (M)

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Fanta Barrow (F)

Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN 55455, USA.

Yi Tao Chan (YT)

Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Helena Lei (H)

Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON M5G 1L7, Canada.

Nicholas K Kotoulas (NK)

Department of Chemistry, University of Toronto, Toronto, ON, Canada.

Juan Jovel (J)

The Applied Genomics Core, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada.

Chiara Pastrello (C)

Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, Toronto, ON M5T 0S8, Canada.

Max Kotlyar (M)

Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, Toronto, ON M5T 0S8, Canada.

Cynthia Goh (C)

Department of Chemistry, University of Toronto, Toronto, ON, Canada.

Evangelos Michelakis (E)

Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Xavier Clemente-Casares (X)

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Pamela S Ohashi (PS)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.

Edgar G Engleman (EG)

School of Medicine, Department of Pathology, Stanford University, Palo Alto, CA, USA.

Shawn Winer (S)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.

Igor Jurisica (I)

Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, Toronto, ON M5T 0S8, Canada; Departments of Medical Biophysics and Computer Science, University of Toronto, Toronto, ON, Canada; Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.

Sue Tsai (S)

Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada. Electronic address: stsai@ualberta.ca.

Daniel A Winer (DA)

Division of Cellular and Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada; Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA. Electronic address: dwiner@buckinstitute.org.

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Classifications MeSH

questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système phagocytaire mononucléé › Cellules dendritiques › Mechanical Stiffness Controls Dendritic Cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Mechanical Stiffness Controls Dendritic Cell...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité innée › Mechanical Stiffness Controls Dendritic Cell...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › Mechanical Stiffness Controls Dendritic Cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Mechanical Stiffness Controls Dendritic Cell...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques cardiovasculaires › Rigidité vasculaire › Mechanical Stiffness Controls Dendritic Cell...