Overexpression of Chromatin Remodeling Factor SRG3 Down-Regulates IL1β-Expressing M1 Macrophages and IL17-Producing T...

The SWItch3-related gene (SRG3) is a core component of ATP-dependent SWI/SNF complexes, which are crucial for regulating immune cell development and function (e.g., macrophages and CD4⁺ T cells), embryonic development, and non-immune cell differentiation. Notably, SRG3 overexpression has been shown to polarize macrophages in the central nervous system toward an anti-inflammatory M2 phenotype, thereby protecting against the development of experimental autoimmune encephalomyelitis in mice. However, the effect of SRG3 on immune responses in adipose tissues remains unclear. To address this issue, we examined the cellularity and inflammatory status of adipose tissue in B10.PL mice overexpressing the SRG3 gene under the ubiquitous β-actin promoter (SRG3^β-actin). Interestingly, SRG3 overexpression significantly reduced adipocyte size in both white and brown adipose tissues, without affecting the overall adipose tissue weight. Such phenotypic effects might be associated with the improved glucose tolerance observed in SRG3^β-actin B10.PL mice. Moreover, we found that SRG3 overexpression down-regulates IL1β-expressing M1 macrophages, leading to a significant decrease in the M1/M2 macrophage ratio. Additionally, SRG3^β-actin B10.PL mice showed a dramatic reduction in neutrophils as well as IL1β- and IL17-producing T cells in adipose tissues. Taken together, our results indicate that SRG3 plays a vital role in maintaining immune homeostasis within adipose tissues.