Suppression of LPS-activated inflammatory responses and chromosomal histone modifications in macrophages by

Qi Chu1,2,3, Weiju Han2,3,4, Zhichun He1,2,3

  • 1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, People's Republic of China.

Insights

Micropatterns suppress macrophage inflammation by altering nuclear shape and chromatin. This leads to increased H3K36me2 methylation, impacting immune cell behavior and gene expression.

Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • Macrophages are key immune cells involved in various physiological and pathological processes.
  • Micropatterns are known to regulate macrophage phenotype by influencing cell shape and mechanical sensing.
  • The nucleus's role as a physical sensor in micropattern-induced cellular responses is often overlooked.

Purpose of the Study:

  • To investigate the role of nuclear deformation in micropattern-mediated regulation of macrophage inflammatory responses.
  • To elucidate the impact of micropatterns on nuclear morphology and chromatin structure in macrophages.
  • To explore the relationship between nuclear changes, histone methylation, and macrophage inflammatory gene expression.

Main Methods:

  • Culturing macrophages on micropatterned and flat surfaces.
  • Analyzing macrophage inflammatory gene expression.
  • Quantifying nuclear volume and chromatin compaction.
  • Measuring histone methylation levels (H3K36me2 and H3K4me3).

Main Results:

  • Macrophages on micropatterned surfaces exhibited suppressed inflammatory gene expression compared to those on flat surfaces.
  • Micropatterned surfaces induced nuclear shrinkage and chromatin compaction in macrophages.
  • Elevated H3K36me2 and decreased H3K4me3 methylation levels were observed in macrophages on micropatterned surfaces.

Conclusions:

  • Nuclear deformation and subsequent H3K36me2 methylation contribute to micropattern-induced suppression of macrophage inflammation.
  • Micropatterns alter macrophage phenotype by influencing nuclear shape and chromatin modifications.
  • This study highlights the nucleus as a critical mediator of micropattern effects on immune cell behavior.