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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number108609
JournalCell reports
Volume34
Issue number2
DOIs
StatePublished - 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

PubMed: MeSH publication types

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

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