Identification of SIN3A as a Promising Epigenetic Target Against Allergic Rhinitis

Hanqiao Li,1– 3 Renkang Wang,1– 3 Benquan Yu,1– 3 Junjie Zeng,1– 3 Zian Xiao1– 3 1Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Institute of Otology, Central South University, Changsha, Hunan Province, People’s Republic of China; 3Laboratory of Otorhinolaryngology Head and Neck Cancer, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Zian Xiao, Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, People’s Republic of China, Email [email protected]: The involvement of histone modifications in the development of other airway allergic diseases has been widely studied and followed, however, the role in allergic rhinitis(AR) has not been explored and discussed.Methods: We downloaded GSE50223 from Gene Expression Omnibus database, obtained histone modification related genes in FACER database, and identified key functional genes related to histone modification in AR by WGCNA and single cell sequencing analysis. Finally, we collected nasal mucosa tissues from AR patients and healthy individuals to verify the expression of the target gene. At the functional level, a co-culture system of house dust mite (HDM)-sensitized human nasal epithelial cells and naive CD4⁺ T cells was employed. Using gene knockdown and overexpression techniques, the role of SIN3A in the differentiation of Th17 and Treg cells was analyzed.Results: SIN3A was identified as a key functional gene related to histone modification with differential expression in AR, and single-cell data analysis showed that SIN3A might be involved in the immune infiltration difference by regulating Treg cells and thus. Upregulation of SIN3A was confirmed in nasal mucosal tissues of AR patients. Functional experiments demonstrated that SIN3A promotes the differentiation of naive T cells into Th17 cells and inhibits their differentiation into Treg cells, thereby disrupting the Th17/Treg balance.Conclusion: Histone modification-related gene SIN3A is differentially expressed in AR and healthy populations. SIN3A may play a significant role in the pathogenesis of AR by regulating the Th17/Treg immune balance. This study first revealed a novel epigenetic mechanism by which SIN3A mediates immune imbalance in allergic rhinitis (AR), providing a theoretical basis for the development of intervention strategies targeting SIN3A.Keywords: allergic rhinitis, histone modification, bioinformatics