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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 8

APOBEC3A and RFX1 regulated the methylation of M1-related genes TNF and IL6.

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APOBEC3A and RFX1 regulated the methylation of M1-related genes TNF and ...
(A and B) The mean methylation levels of CpG sites within TNF (A) and IL6 (B) promoters in hMDMs infected with pLV-NC or pLV-APOBEC3A (n = 4 per group). (C and D) The mean methylation levels of CpG sites within TNF (C) and IL6 (D) promoters in M1 hMDMs infected with pLV-NC or pLV-RFX1 (n = 4 per group). (E and F) The mean methylation levels of CpG sites within TNF (E) and IL6 (F) promoters in CD14+ monocytes from HC or patients with SLE (n = 5 per group). (G and H) The mean methylation levels of CpG sites within TNF (G) and IL6 (H) in M1 hMDMs from HC or patients with SLE (n = 6 per group). Ten respective clones from each group were sequenced. Data represent mean ± SEM, using 2-tailed Student’s t test. *P < 0.05, **P < 0.01, ***P < 0.001.

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