Ubiquitous Overexpression of Chromatin Remodeling Factor SRG3 Exacerbates Atopic Dermatitis in NC/Nga Mice by Enhancing Th2 Immune Responses

• Published in: International journal of molecular sciences Vol. 22; no. 4; p. 1553
• Main Authors: Lee, Sung Won, Park, Hyun Jung, Jeon, Jungmin, Park, Yun Hoo, Kim, Tae-Cheol, Jeon, Sung Ho, Seong, Rho Hyun, Van Kaer, Luc, Hong, Seokmann
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.02.2021; MDPI
• Subjects: Actin; Actins - metabolism; Animals; Atopic dermatitis; Biopsy; Chromatin Assembly and Disassembly; Chromatin remodeling; Cytokines; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dermatitis; Dermatitis, Atopic - diagnosis; Dermatitis, Atopic - etiology; Dermatitis, Atopic - metabolism; Disease; Disease Models, Animal; Disease Susceptibility; Eczema; Experimental allergic encephalomyelitis; Gene Expression; Genotype & phenotype; Helper cells; Immune response; Immunity, Cellular; Immunoglobulin E; Inflammation; Interleukin 4; Leukocytes (basophilic); Lymphocytes; Lymphocytes T; Macrophages; Macrophages - immunology; Macrophages - metabolism; Mast cells; Mice; Mice, Transgenic; NC/Nga; Pathogenesis; Rodents; Severity of Illness Index; Skin diseases; Skin lesions; Spleen; Sucrose; SWI3-related gene (SRG3); Th2 cells; Th2 Cells - immunology; Th2 Cells - metabolism; Transcription Factors - genetics; Transgenic mice; Treg cells; Treg cells; atopic dermatitis; Th2 cells; WT; NC/Nga; SWI3-related gene (SRG3)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22041553

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3 mice). We found that SRG3 NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3 NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.