2. Academic Validation
  3. Interfering with alternatively activated macrophages by CSF-1R inhibition exerts therapeutic capacity on allergic airway inflammation

Interfering with alternatively activated macrophages by CSF-1R inhibition exerts therapeutic capacity on allergic airway inflammation

  • Biochem Pharmacol. 2022 Apr;198:114952. doi: 10.1016/j.bcp.2022.114952.
Caigui Xiang 1,  Chen Fan 2,  Qiukai Lu 1,  Moting Liu 1,  Huimin Lu 1,  Chunlan Feng 2,  Yanwei Wu 2,  Bing Wu 1,  Heng Li 3,  Wei Tang 4
Affiliations

Affiliations

  • 1 Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: [email protected].
  • 4 Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
PMID: 35149050 DOI: 10.1016/j.bcp.2022.114952
Abstract

Purpose: Allergic asthma is a chronic inflammatory disorder with airway hyperresponsiveness and tissue remodeling as the main pathological characteristics. The etiology of asthma is relatively complicated, involving genetic susceptibility, epigenetic regulation, environmental factors, and immune imbalance. Colony stimulating factor 1 receptor (CSF-1R), highly expressed in myeloid monocytes, plays an important role in regulating inflammation. However, the pathological role of CSF-1R and the therapeutic effects of CSF-1R inhibitor in allergic airway inflammation remain indistinct.

Methods: The house dust Mite (HDM)-triggered allergic airway inflammation model was conducted to fully uncover the efficacies of CSF-1R inhibition, as illustrated by histopathological examinations, biochemical analysis, ELISA, RT-PCR, Western blotting assay, immunofluorescence, and flow cytometry. Furthermore, bone marrow-derived macrophages (BMDMs) were differentiated and polarized upon IL-4/IL-13 induction to clarify the underlying mechanisms of CSF-1R inhibition.

Results: Herein, we presented that the expression of CSF-1R was increased in HDM-induced experimental asthma and inhibition of CSF-1R displayed dramatic effects on the disease severity of asthma, referring to suppressing the secretion of allergic mediators, dysfunction of airway epithelium, and infiltration of inflammatory cells. Furthermore, CSF-1R inhibitor could markedly restrain the polarization and expression of transcriptional factors of alternatively activated macrophages (AAMs) in the presence of IL-4/IL-13 and reduce the recruitment of CSF-1R-dominant macrophages, both in acute and chronic allergic airway inflammation model.

Conclusion: Collectively, our findings demonstrated the molecular pathological mechanism of CSF-1R in allergic airway diseases and suggested that targeting CSF-1R might be an alternative intervention strategy on the homeostasis of airway immune microenvironment in asthma.

Keywords

Allergy; Asthma; CSF-1R; Inflammation; Macrophages.

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