Regulatory factor X1 induces macrophage M1 polarization by promoting DNA demethylation in autoimmune inflammation
Shuang Yang, Pei Du, Haobo Cui, Meiling Zheng, Wei He, Xiaofei Gao, Zhi Hu, Sujie Jia, Qianjin Lu, Ming Zhao
Shuang Yang, Pei Du, Haobo Cui, Meiling Zheng, Wei He, Xiaofei Gao, Zhi Hu, Sujie Jia, Qianjin Lu, Ming Zhao
View: Text | PDF
Research Article Inflammation

Regulatory factor X1 induces macrophage M1 polarization by promoting DNA demethylation in autoimmune inflammation

Abstract

Abnormal macrophage polarization is generally present in autoimmune diseases. Overwhelming M1 macrophage activation promotes the continuous progression of inflammation, which is one of the reasons for the development of autoimmune diseases. However, the underlying mechanism is still unclear. Here we explore the function of Regulatory factor X1 (RFX1) in macrophage polarization by constructing colitis and lupus-like mouse models. Both in vivo and in vitro experiments confirmed that RFX1 can promote M1 and inhibit M2 macrophage polarization. Furthermore, we found that RFX1 promoted DNA demethylation of macrophage polarization–related genes by increasing APOBEC3A/Apobec3 expression. We identified a potential RFX1 inhibitor, adenosine diphosphate (ADP), providing a potential strategy for treating autoimmune diseases.

Authors

Shuang Yang, Pei Du, Haobo Cui, Meiling Zheng, Wei He, Xiaofei Gao, Zhi Hu, Sujie Jia, Qianjin Lu, Ming Zhao

×

Figure 3

Rfx1 KO inhibited M1 macrophage polarization.

Options: View larger image (or click on image) Download as PowerPoint
Rfx1 KO inhibited M1 macrophage polarization. (A and B) The mRNA (n = 3...
(A and B) The mRNA (n = 3 each group) (A) and protein (B) expressions of RFX1 in PMAs from Rfx1fl/fl (WT) and Rfx1fl/flLyz2-Cre (CKO) mice, respectively. (C) Volcano plot of differently expressed genes between LPS-induced M1 PMAs from WT or CKO mice (n = 3 each group). (D) Heatmap revealed differentially expressed macrophage polarization–related genes between M1 PMAs from WT and CKO mice. (E) Enrichment analysis of differentially expressed genes in WT or CKO group based on GSEA pathway database. (F and G) Significantly enriched GO terms (F) and KEGG pathways (G) of downregulated genes in M1 PMAs from CKO mice. |Log2FC|≥1 and P ≤ 0.05 are the screening criteria for differential genes detected by RNA-Seq between 2 groups. (H and I) The relative mRNA (H) and protein expressions in culture supernatant (I) of M1-related genes Tnf, Il6, and Il1b were detected by qPCR and ELISA (n = 4 each group). (J) The relative expression of the indicated M2-related genes in M1 PMAs from WT and CKO mice (n = 4 each group). (K) Representative flow cytometry histograms and mean fluorescence intensities (MFI) statistics of Arg-1 and CD206 (n = 3 each group). Data represent mean ± SEM, using 2-tailed Student’s t test for A and H–K. *P < 0.05, **P < 0.01, ***P < 0.001.