Neutrophil-modulated Dicer expression in macrophages influences inflammation resolution.

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Tác giả: Hong Chen, Tao Huang, Xinyi Huang, Jialin Jia, Tianrong Jin, Jia Li, Wenhua Li, Yongsheng Li, Feihong Liang, Shengran Liu, Tingting Liu, Yu Liu, Bangwei Luo, Huishan Wang, Zhishang Wang, Xiaodong Xue, Liming Yu, Zhiren Zhang, Jikai Zhao

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Switzerland : Cellular and molecular life sciences : CMLS , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 703910

The precise molecular mechanisms through which neutrophils regulate macrophages in the progression and resolution of acute inflammation remain poorly understood. Here, we present new findings on the role of Dicer in regulating macrophage phenotypic transitions essential for proper inflammatory progression and resolution, influenced by neutrophils. Using a zymosan A (Zym A)-induced self-limited mouse peritonitis model, we observed that Dicer expression in macrophages was significantly reduced by neutrophil-derived IFN-γ during the progression phase, but gradually returned to normal levels during the resolution phase following the engulfment of apoptotic neutrophils. Our study on macrophage-specific Dicer1-depletion (Dicer1-CKO) mice demonstrated that inflammation in these mice was more severe during the progression phase, characterized by increased pro-inflammatory cytokines and enhanced neutrophil trafficking. Additionally, resolution was impaired in Dicer1-CKO mice, leading to the accumulation of uncleared apoptotic neutrophils. Specifically, the absence of Dicer in macrophages resulted in M1 polarization and heightened bactericidal activity, facilitating the progression of acute inflammation. Conversely, inducing Dicer expression promoted macrophage transition to M2 polarization, enhancing apoptotic cell clearance and expediting the resolution of inflammation. Our findings suggest that Dicer plays a central role in regulating the progression and resolution of acute inflammation, with implications for the treatment of inflammatory diseases.
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