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Mechanical Stiffness Controls Dendritic Cell Metabolism and Function.
Chakraborty, Mainak; Chu, Kevin; Shrestha, Annie; Revelo, Xavier S; Zhang, Xiangyue; Gold, Matthew J; Khan, Saad; Lee, Megan; Huang, Camille; Akbari, Masoud; Barrow, Fanta; Chan, Yi Tao; Lei, Helena; Kotoulas, Nicholas K; Jovel, Juan; Pastrello, Chiara; Kotlyar, Max; Goh, Cynthia; Michelakis, Evangelos; Clemente-Casares, Xavier; Ohashi, Pamela S; Engleman, Edgar G; Winer, Shawn; Jurisica, Igor; Tsai, Sue; Winer, Daniel A.
Afiliación
  • 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.
  • Chu K; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
  • 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.
  • 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.
  • Zhang X; School of Medicine, Department of Pathology, Stanford University, Palo Alto, CA, USA.
  • Gold MJ; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
  • 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.
  • Lee M; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
  • Huang C; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
  • Akbari M; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
  • Barrow F; Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN 55455, USA.
  • Chan YT; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • 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.
  • Kotoulas NK; Department of Chemistry, University of Toronto, Toronto, ON, Canada.
  • Jovel J; The Applied Genomics Core, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada.
  • 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.
  • 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.
  • Goh C; Department of Chemistry, University of Toronto, Toronto, ON, Canada.
  • Michelakis E; Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
  • Clemente-Casares X; Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
  • 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.
  • Engleman EG; School of Medicine, Department of Pathology, Stanford University, Palo Alto, CA, USA.
  • 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.
  • 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, Universi
  • 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.
  • 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 Immu
Cell Rep ; 34(2): 108609, 2021 01 12.
Article en En | MEDLINE | ID: mdl-33440149
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 Ca2+-related ion channels, including potentially PIEZO1, as important effectors impacting DC metabolism and function under tension. Tension also directs the phenotypes of monocyte-derived DCs in humans. Thus, mechanical stiffness is a critical environmental cue of DCs and innate immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Rigidez Vascular / Inmunidad Innata / Inmunoterapia Límite: Humans Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Rigidez Vascular / Inmunidad Innata / Inmunoterapia Límite: Humans Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos