2. Academic Validation
  3. Neutrophil-modulated Dicer expression in macrophages influences inflammation resolution

Neutrophil-modulated Dicer expression in macrophages influences inflammation resolution

  • Cell Mol Life Sci. 2025 Mar 13;82(1):114. doi: 10.1007/s00018-025-05644-6.
Zhishang Wang # 1,  Wenhua Li # 2,  Jia Li # 3,  Tianrong Jin 4,  Hong Chen 5,  Feihong Liang 6,  Shengran Liu 2,  Jialin Jia 2,  Tingting Liu 2,  Yu Liu 2,  Liming Yu 1,  Xiaodong Xue 1,  Jikai Zhao 1,  Tao Huang 1,  Xinyi Huang 1,  Huishan Wang 7,  Yongsheng Li 8,  Bangwei Luo 9,  Zhiren Zhang 10
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenhe District, Shenyang, Liaoning, 110016, China.
  • 2 Institute of Immunology, Army Medical University, 30 Gaotanyan Main Street, Chongqing, 400038, China.
  • 3 Department of Nephrology, Navy 971 Hospital, 22 Minjiang Road, Qingdao, Shandong, 266000, China.
  • 4 Medical College of Chongqing University, Chongqing, 400030, China.
  • 5 Department of Orthopedics, No. 903 Hospital of PLA Joint Logistic Support Force, 14 Lingyin Road, Lingyin Street, Xihu District, Hangzhou, Zhejiang, 310000, China.
  • 6 Department of Medical Science, Shunde Polytechnic, Foshan, China.
  • 7 Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenhe District, Shenyang, Liaoning, 110016, China. huishanw@126.com.
  • 8 Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, China. lys@cqu.edu.cn.
  • 9 Institute of Immunology, Army Medical University, 30 Gaotanyan Main Street, Chongqing, 400038, China. luo6341@tmmu.edu.cn.
  • 10 Institute of Immunology, Army Medical University, 30 Gaotanyan Main Street, Chongqing, 400038, China. zhangzhiren@tmmu.edu.cn.
  • # Contributed equally.
PMID: 40074991 DOI: 10.1007/s00018-025-05644-6
Abstract

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.

Keywords

Dicer; Efferocytosis; IFN-γ; Inflammation resolution; Macrophage polarization; Neutrophil.

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