Mechanical Stiffness Controls Dendritic Cell Metabolism and Function

Mainak Chakraborty; Kevin Chu; Annie Shrestha; Xavier S. Revelo; Xiangyue Zhang; Matthew J. Gold; Saad Khan; Megan Lee; Camille Huang; Masoud Akbari; Fanta Barrow; Yi Tao Chan; Helena Lei; Nicholas K. Kotoulas; Juan Jovel; Chiara Pastrello; Max Kotlyar; Cynthia Goh; Evangelos Michelakis; Xavier Clemente-Casares; Pamela S. Ohashi; Edgar G. Engleman; Shawn Winer; Igor Jurisica; Sue Tsai; Daniel A. Winer

doi:10.1016/j.celrep.2020.108609

Mechanical Stiffness Controls Dendritic Cell Metabolism and Function

Mainak Chakraborty, Kevin Chu, Annie Shrestha, Xavier S. Revelo, Xiangyue Zhang, Matthew J. Gold, Saad Khan, Megan Lee, Camille Huang, Masoud Akbari, Fanta Barrow, Yi Tao Chan, Helena Lei, Nicholas K. Kotoulas, Juan Jovel, Chiara Pastrello, Max Kotlyar, Cynthia Goh, Evangelos Michelakis, Xavier Clemente-CasaresPamela S. Ohashi, Edgar G. Engleman, Shawn Winer, Igor Jurisica, Sue Tsai, Daniel A. Winer

Physiology

Research output: Contribution to journal › Article › peer-review

95 Scopus citations

Abstract

The immune system is carefully tuned to respond to dangers in the environment. Chakraborty et al. show that environmental stiffness controls dendritic cell metabolism, phenotype, and inflammatory function through downstream Hippo-signaling mediators. The findings provide evidence for mechanical force as an integral node directing innate immune responses.

Original language	English (US)
Article number	108609
Journal	Cell reports
Volume	34
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2020.108609
State	Published - Jan 12 2021

Bibliographical note

Funding Information:
We thank Dr. Darren Yuen for discussions in preparing the hydrogels, Dr. Battsetseg Batchuluun (Dr. Michael Wheeler Lab) for assistance with the calcium assays, and Christina Lam for assistance in processing tumor samples. The tetramers were supplied by the NIH Tetramer Core Facility. S.K. is a recipient of the Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST)/Aventis Pasteur and the Banting and Best Diabetes Centre (BBDC)-Novo Nordisk Studentship. S.T. is a recipient of the National Research Council H.L. Holmes Postdoctoral Fellowship and a Tier 2 Canada Research Chair in Immunometabolism and Diabetes. She is funded by the Li Ka Shing Institute of Virology Bridge Fund and New Frontiers in Research-Exploration Fund . D.A.W. is funded by Canadian Institutes of Health Research (CIHR) New Investigator Foundation Grant FDN-148385 and the Huiying Memorial Foundation . D.A.W. has an Ontario Ministry of Innovation Early Researcher Award. Computational analyses (I.J.) were in part supported by the grants from the Ontario Research Fund ( 34876 ), Natural Sciences Research Council (NSERC; 203475 ), Canada Foundation for Innovation (CFI; 29272 , 225404 , and 33536 ), Buchan Foundation , and IBM .

Funding Information:
We thank Dr. Darren Yuen for discussions in preparing the hydrogels, Dr. Battsetseg Batchuluun (Dr. Michael Wheeler Lab) for assistance with the calcium assays, and Christina Lam for assistance in processing tumor samples. The tetramers were supplied by the NIH Tetramer Core Facility. S.K. is a recipient of the Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST)/Aventis Pasteur and the Banting and Best Diabetes Centre (BBDC)-Novo Nordisk Studentship. S.T. is a recipient of the National Research Council H.L. Holmes Postdoctoral Fellowship and a Tier 2 Canada Research Chair in Immunometabolism and Diabetes. She is funded by the Li Ka Shing Institute of Virology Bridge Fund and New Frontiers in Research-Exploration Fund. D.A.W. is funded by Canadian Institutes of Health Research (CIHR) New Investigator Foundation Grant FDN-148385 and the Huiying Memorial Foundation. D.A.W. has an Ontario Ministry of Innovation Early Researcher Award. Computational analyses (I.J.) were in part supported by the grants from the Ontario Research Fund (34876), Natural Sciences Research Council (NSERC; 203475), Canada Foundation for Innovation (CFI; 29272, 225404, and 33536), Buchan Foundation, and IBM. S.T. M.C. K.C. A.S. X.S.R. X.Z. M.J.G. S.K. H.L. M.A. F.B. Y.T.C. N.K.K. X.C.-C. M.K. C.P. M.L. and C.H. performed experiments and analyzed and interpreted data. A.S. C.G. P.S.O. E.G.E. X.S.R. E.M. I.J. and S.W. provided feedback and supervised aspects of the study. S.W. and D.A.W. conceived the study. I.J. provided data analysis support. S.T. and D.A.W. contributed to the experimental design, analysis, and writing of the manuscript and supervised the overall implementation of the study. All authors contributed to revision of the manuscript. The authors declare no competing interests.

Publisher Copyright:
© 2020 The Author(s)

Keywords

PIEZO1
TAZ
danger signals
dendritic cells
immunometabolism
inflammation
innate immunity
mechanoimmunology
mechanosensing
tension

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Chakraborty, M., Chu, K., Shrestha, A., Revelo, X. S., Zhang, X., Gold, M. J., Khan, S., Lee, M., Huang, C., Akbari, M., Barrow, F., Chan, Y. T., Lei, H., Kotoulas, N. K., Jovel, J., Pastrello, C., Kotlyar, M., Goh, C., Michelakis, E., ... Winer, D. A. (2021). Mechanical Stiffness Controls Dendritic Cell Metabolism and Function. Cell reports, 34(2), Article 108609. https://doi.org/10.1016/j.celrep.2020.108609

Chakraborty, M, Chu, K, Shrestha, A, Revelo, XS, Zhang, X, Gold, MJ, Khan, S, Lee, M, Huang, C, Akbari, M, Barrow, F, Chan, YT, Lei, H, Kotoulas, NK, Jovel, J, Pastrello, C, Kotlyar, M, Goh, C, Michelakis, E, Clemente-Casares, X, Ohashi, PS, Engleman, EG, Winer, S, Jurisica, I, Tsai, S & Winer, DA 2021, 'Mechanical Stiffness Controls Dendritic Cell Metabolism and Function', Cell reports, vol. 34, no. 2, 108609. https://doi.org/10.1016/j.celrep.2020.108609

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abstract = "The immune system is carefully tuned to respond to dangers in the environment. Chakraborty et al. show that environmental stiffness controls dendritic cell metabolism, phenotype, and inflammatory function through downstream Hippo-signaling mediators. The findings provide evidence for mechanical force as an integral node directing innate immune responses.",

keywords = "PIEZO1, TAZ, danger signals, dendritic cells, immunometabolism, inflammation, innate immunity, mechanoimmunology, mechanosensing, tension",

author = "Mainak Chakraborty and Kevin Chu and Annie Shrestha and Revelo, {Xavier S.} and Xiangyue Zhang and Gold, {Matthew J.} and Saad Khan and Megan Lee and Camille Huang and Masoud Akbari and Fanta Barrow and Chan, {Yi Tao} and Helena Lei and Kotoulas, {Nicholas K.} and Juan Jovel and Chiara Pastrello and Max Kotlyar and Cynthia Goh and Evangelos Michelakis and Xavier Clemente-Casares and Ohashi, {Pamela S.} and Engleman, {Edgar G.} and Shawn Winer and Igor Jurisica and Sue Tsai and Winer, {Daniel A.}",

note = "Funding Information: We thank Dr. Darren Yuen for discussions in preparing the hydrogels, Dr. Battsetseg Batchuluun (Dr. Michael Wheeler Lab) for assistance with the calcium assays, and Christina Lam for assistance in processing tumor samples. The tetramers were supplied by the NIH Tetramer Core Facility. S.K. is a recipient of the Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST)/Aventis Pasteur and the Banting and Best Diabetes Centre (BBDC)-Novo Nordisk Studentship. S.T. is a recipient of the National Research Council H.L. Holmes Postdoctoral Fellowship and a Tier 2 Canada Research Chair in Immunometabolism and Diabetes. She is funded by the Li Ka Shing Institute of Virology Bridge Fund and New Frontiers in Research-Exploration Fund . D.A.W. is funded by Canadian Institutes of Health Research (CIHR) New Investigator Foundation Grant FDN-148385 and the Huiying Memorial Foundation . D.A.W. has an Ontario Ministry of Innovation Early Researcher Award. Computational analyses (I.J.) were in part supported by the grants from the Ontario Research Fund ( 34876 ), Natural Sciences Research Council (NSERC; 203475 ), Canada Foundation for Innovation (CFI; 29272 , 225404 , and 33536 ), Buchan Foundation , and IBM . Funding Information: We thank Dr. Darren Yuen for discussions in preparing the hydrogels, Dr. Battsetseg Batchuluun (Dr. Michael Wheeler Lab) for assistance with the calcium assays, and Christina Lam for assistance in processing tumor samples. The tetramers were supplied by the NIH Tetramer Core Facility. S.K. is a recipient of the Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST)/Aventis Pasteur and the Banting and Best Diabetes Centre (BBDC)-Novo Nordisk Studentship. S.T. is a recipient of the National Research Council H.L. Holmes Postdoctoral Fellowship and a Tier 2 Canada Research Chair in Immunometabolism and Diabetes. She is funded by the Li Ka Shing Institute of Virology Bridge Fund and New Frontiers in Research-Exploration Fund. D.A.W. is funded by Canadian Institutes of Health Research (CIHR) New Investigator Foundation Grant FDN-148385 and the Huiying Memorial Foundation. D.A.W. has an Ontario Ministry of Innovation Early Researcher Award. Computational analyses (I.J.) were in part supported by the grants from the Ontario Research Fund (34876), Natural Sciences Research Council (NSERC; 203475), Canada Foundation for Innovation (CFI; 29272, 225404, and 33536), Buchan Foundation, and IBM. S.T. M.C. K.C. A.S. X.S.R. X.Z. M.J.G. S.K. H.L. M.A. F.B. Y.T.C. N.K.K. X.C.-C. M.K. C.P. M.L. and C.H. performed experiments and analyzed and interpreted data. A.S. C.G. P.S.O. E.G.E. X.S.R. E.M. I.J. and S.W. provided feedback and supervised aspects of the study. S.W. and D.A.W. conceived the study. I.J. provided data analysis support. S.T. and D.A.W. contributed to the experimental design, analysis, and writing of the manuscript and supervised the overall implementation of the study. All authors contributed to revision of the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020 The Author(s)",

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doi = "10.1016/j.celrep.2020.108609",

language = "English (US)",

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AU - Chakraborty, Mainak

AU - Chu, Kevin

AU - Shrestha, Annie

AU - Revelo, Xavier S.

AU - Zhang, Xiangyue

AU - Gold, Matthew J.

AU - Khan, Saad

AU - Lee, Megan

AU - Huang, Camille

AU - Akbari, Masoud

AU - Barrow, Fanta

AU - Chan, Yi Tao

AU - Lei, Helena

AU - Kotoulas, Nicholas K.

AU - Jovel, Juan

AU - Pastrello, Chiara

AU - Kotlyar, Max

AU - Goh, Cynthia

AU - Michelakis, Evangelos

AU - Clemente-Casares, Xavier

AU - Ohashi, Pamela S.

AU - Engleman, Edgar G.

AU - Winer, Shawn

AU - Jurisica, Igor

AU - Tsai, Sue

AU - Winer, Daniel A.

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Y1 - 2021/1/12

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KW - TAZ

KW - danger signals

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KW - immunometabolism

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KW - innate immunity

KW - mechanoimmunology

KW - mechanosensing

KW - tension

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Mechanical Stiffness Controls Dendritic Cell Metabolism and Function

Abstract

Bibliographical note

Keywords

UN SDGs

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