Page 80 - ebook

[B. Cell Biology/Stem Cell] B-40

F-actin-mediated mechanosensation controls STAT6-

dependent M2 macrophage activation

Jeong-Ki Kim¹, Dong-Hwee Kim¹,²*

¹KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea,

²Department of Integrative Energy Engineering, College of Engineering, Korea University, Seoul 02841, Korea

Macrophages play an important role in inflammation and immune responses, and their malfunctioning is highly

associated with the progression of various human diseases. The alternatively activated or M2 macrophages, deemed
benign opposites of 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, however, the mechanism of how the varying extracellular mechanical conditions
alter their immunological activation remains unclear. Here, we present that M2 activation requires threshold

mechanical cue of the extracellular microenvironment, and matrix rigidity dependent macrophage spreading is
mediated by F-actin formation, which 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, where intranuclear transportation of STAT6 is promoted by the rigid matrix

that facilitates F-actin formation. Our findings reveal that F-actin-mediated mechanosensation can act as an
immunomodulatory pathway to determine the M2 activation of macrophages triggered by anti-inflammatory factors,
providing a new perspective on the relationship between physical cues and immune responses.