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
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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

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Figure 4

RFX1 overexpression promoted M1 macrophage polarization.

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RFX1 overexpression promoted M1 macrophage polarization. (A and B) The r...
(A and B) The relative mRNA (n = 6) (A) and protein (B) expressions of RFX1 in LPS-induced M1 PMAs infected with pLV-NC and pLV-Rfx1. (C) Volcano plot of differently expressed genes between M1 PMAs transfected with pLV-NC and pLV-Rfx1 (n = 3). (D) Heatmap indicated differentially expressed macrophage polarization–related genes between M1 PMAs infected with pLV-NC and pLV-Rfx1. (E) GSEA pathway database was used to detect enrichment plots of differently expressed genes in each group. (F and G) Significantly enriched GO terms (F) and KEGG pathways (G) in M1 PMAs infected with pLV-Rfx1. |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 expressions (H) (n = 4) and the protein concentrations (I) (n = 3) in culture supernatant of TNF-α, IL-6, and IL-1β in PMAs were detected. (J) The relative mRNA levels of the indicated M2-related genes in M1 PMAs infected with pLV-NC and pLV-Rfx1 (n = 4). (K) Representative flow cytometry histograms and MFI statistics of Arg-1 and CD206 in each group (n = 3). Data represent mean ± SEM; 2-tailed Student’s t test was used for A and H–K. *P < 0.05, **P < 0.01.