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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

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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 1

RFX1 expression was increased in inflammatory diseases.

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RFX1 expression was increased in inflammatory diseases.
(A) The relative...
(A) The relative mRNA expression of Rfx1, Il1b, Tnf, and Il6 in colon from control (NC) and colitis (DSS) mice (n = 6 each group). (B) Representative images of IF staining of indicated positive cells in colon from control (NC) or colitis (DSS) mice. Scale bar: 50 mm. (C) The relative mRNA expression of RFX1 in CD14+ monocyte from healthy controls (HC) and patients with SLE (n = 18 each group). (D) Western blot was used to detect the protein expression of RFX1 in CD14+ monocytes from HC and patients with SLE (n = 6 each group). The protein expression was normalized to GAPDH. Data represent mean ± SEM, 2-tailed Student’s t test. *P < 0.05, **P < 0.01, ***P < 0.001.

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