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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Macrophages*/metabolism ; Macrophages*/immunology ; Interleukin-1beta*/metabolism ; Interleukin-1beta*/genetics ; Adipose Tissue*/metabolism ; Interleukin-17*/metabolism ; Interleukin-17*/genetics; Animals ; Mice ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Down-Regulation ; Chromatin Assembly and Disassembly ; Male ; T-Lymphocytes/metabolism ; T-Lymphocytes/immunology

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.
Competing Interests: L.V.K. is a member of the scientific advisory board of Isu Abxis Co., Ltd. (Republic of Korea). The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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NRF-2021R1I1A1A01054418 National Research Foundation of Korea; NRF-2019R1A2C1009926 National Research Foundation of Korea; NRF-2022R1A2C1009590 National Research Foundation of Korea

Keywords: IL17; M1 macrophage; SWItch3-related gene (SRG3); adipose tissue; glucose tolerance

0 (Interleukin-1beta)
0 (Interleukin-17)
0 (Transcription Factors)
0 (IL1B protein, mouse)

Date Created: 20241109 Date Completed: 20241109 Latest Revision: 20241116

20241116

PMC11546064

10.3390/ijms252111681

39519233