2. Academic Validation
  3. TREM2 Insufficiency Protects against Pulmonary Fibrosis by Inhibiting M2 Macrophage Polarization

TREM2 Insufficiency Protects against Pulmonary Fibrosis by Inhibiting M2 Macrophage Polarization

  • Int Immunopharmacol. 2023 Mar 30;118:110070. doi: 10.1016/j.intimp.2023.110070.
Qiujie Luo 1,  Dawei Deng 1,  Yang Li 1,  Hongjie Shi 1,  Jinping Zhao 1,  Qiaofeng Qian 1,  Wei Wang 1,  Jie Cai 1,  Wenjun Yu 2,  Jinping Liu 3
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan 430071, China; Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan 430071, China.
  • 2 Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan 430071, China; Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan 430071, China. Electronic address: [email protected].
  • 3 Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; Hubei Provincial Engineering Research Center of Minimally Invasive Cardiovascular Surgery, Wuhan 430071, China; Wuhan Clinical Research Center for Minimally Invasive Treatment of Structural Heart Disease, Wuhan 430071, China. Electronic address: [email protected].
PMID: 37003186 DOI: 10.1016/j.intimp.2023.110070
Abstract

Rationale Idiopathic pulmonary fibrosis (IPF) is a lung disease with high mortality, limited treatment options and an unknown aetiology. M2 macrophages play a critical role in the pathological process of IPF. Triggering receptor expressed on myeloid cells-2 (TREM2) participates in the regulation of macrophages, although its role in IPF remains elusive.

Methods: This study examined the role of TREM2 in macrophage regulation using a well-established bleomycin (BLM)-induced pulmonary fibrosis (PF) mouse model. TREM2 insufficiency was induced by intratracheal treatment with TREM2-specific siRNA. The effects of TREM2 on IPF were evaluated using histological staining and molecular biological methods.

Results: TREM2 expression levels were significantly elevated in the lungs of IPF patients and mice with BLM-induced pulmonary fibrosis mice. Bioinformatics analysis revealed that IPF patients with higher TREM2 expression had a shorter survival time, and that TREM2 expression was closely associated with fibroblasts and M2 macrophages. Gene Ontology (GO) enrichment analysis showed that found TREM2-related differentially expressed genes (DEGs) were associated with inflammatory responses, extracellular matrix (ECM) and collagen formation. Single-cell RNA sequencing analysis revealed that TREM2 was predominantly expressed in macrophages. TREM2 insufficiency inhibited BLM-induced pulmonary fibrosis and M2 macrophage polarization. Mechanistic studies showed that TREM2 insufficiency suppressed the activation of STAT6 and the expression of fibrotic factors such as Fibronectin (Fib), Collagen I (Col I) and α- smooth muscle actin (α-SMA).

Conclusion: Our study showed that TREM2 insufficiency might alleviate pulmonary fibrosis possibly through macrophage polarization regulation via STAT6 activation, providing a promising macrophage-related approach for the clinical therapy of pulmonary fibrosis.

Keywords

Fibrosis; M2 macrophage; Macrophage polarization; Pulmonary fibrosis; Triggering receptor expressed on myeloid cells 2 (TREM2).

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