Kim, Jeong-Ki Han, Seong-Beom Park, Serk In Kim, In San Kim, Dong-Hwee Kim 2024-01-12T02:35:40Z 2024-01-12T02:35:40Z 2022-11-03 2022-11 0142-9612 https://pubs.kist.re.kr/handle/201004/75950 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. English Pergamon Press Ltd. Nuclear transport of STAT6 determines the matrix rigidity dependent M2 activation of macrophages Article 10.1016/j.biomaterials.2022.121859 1 Biomaterials, v.290 Biomaterials 290 N scie scopus 000878693500003 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article TRANSCRIPTIONAL REGULATION SUBSTRATE STIFFNESS CELL POLARIZATION DIVERSITY RESPONSES PATHWAYS PROTEINS FORCES M2 macrophage STAT6 Nuclear transport Mechanosensation Nuclear mechanics Mechanomodulation of immune response