Nuclear transport of STAT6 determines the matrix rigidity dependent M2 activation of macrophages

Jeong Ki Kim, Seong Beom Han, Serk In Park, In San Kim, Dong Hwee Kim

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Alternatively activated or M2 macrophages, as opposed to the well characterized pro-inflammatory or M1 macrophages, vitally regulate anti-inflammation, wound healing, and tissue repair to maintain tissue homeostasis. Although ubiquitous presence of macrophages in diverse tissues, exposed to different physical environments, infers distinct immune responses of M2 macrophages with high phenotypic heterogeneity, the underlying mechanism of how the varying extracellular mechanical conditions alter their immunological activation remains unclear. Here, we demonstrate that M2 activation requires a threshold mechanical cue from the extracellular microenvironment, and matrix rigidity-dependent macrophage spreading is mediated by the F-actin formation that is essential to regulate mechanosensitive M2 activation of macrophages. We identified a new mechanosensing function of STAT6 (signal transducer and activator of transcription 6), a key transcription factor for M2 activation, whose intranuclear transportation is promoted by the rigid matrix that facilitates the F-actin formation. Our findings further highlight the critical role of mechanosensitive M2 activation of macrophages in long-term adaptation to the extracellular microenvironment by bridging nuclear mechanosensation and immune responses.

Original languageEnglish
Article number121859
JournalBiomaterials
Volume290
DOIs
Publication statusPublished - 2022 Nov

Bibliographical note

Funding Information:
D.K. was supported by the National Research Foundation of Korea ( NRF-2019R1A2C2004437 , NRF-2020R1A4A3079755 , and NRF-2022M3H4A1A03067401 ) and the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program ( IITP-2020-0-01819 ) supervised by the IITP (Institute for Information & communications Technology Planning & Evaluation).

Funding Information:
The authors thank the members of the Applied Mechanobiology Group (AMG) at Korea University for constructive discussion of cellular mechanobiology. This work was supported by the KU-KIST Graduate School of Converging Science and Technology Program.

Funding Information:
D.K. was supported by the National Research Foundation of Korea (NRF-2019R1A2C2004437, NRF-2020R1A4A3079755, and NRF-2022M3H4A1A03067401) and the MSIT (Ministry of Science and ICT), Korea, under the ICT Creative Consilience program (IITP-2020-0-01819) supervised by the IITP (Institute for Information & communications Technology Planning & Evaluation).The authors thank the members of the Applied Mechanobiology Group (AMG) at Korea University for constructive discussion of cellular mechanobiology. This work was supported by the KU-KIST Graduate School of Converging Science and Technology Program.

Publisher Copyright:
© 2022 The Authors

Keywords

  • M2 macrophage
  • Mechanomodulation of immune response
  • Mechanosensation
  • Nuclear mechanics
  • Nuclear transport
  • STAT6

ASJC Scopus subject areas

  • Mechanics of Materials
  • Ceramics and Composites
  • Bioengineering
  • Biophysics
  • Biomaterials

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