CXCL10 modulates airway inflammation in asthma via Sirt3-dependent macrophage homeostasis

Wenqian Ding; Pingping Wang; Zhenyu Ding; Beibei Yang; Shaohu Huo; Paiyu Lin; Jiaying Zhao; Yuanhong Xu; Shenggang Ding

doi:10.1016/j.lfs.2025.123849

CXCL10 modulates airway inflammation in asthma via Sirt3-dependent macrophage homeostasis

Life Sci. 2025 Jul 10:123849. doi: 10.1016/j.lfs.2025.123849. Online ahead of print.

Authors

Wenqian Ding¹, Pingping Wang¹, Zhenyu Ding², Beibei Yang¹, Shaohu Huo¹, Paiyu Lin¹, Jiaying Zhao¹, Yuanhong Xu³, Shenggang Ding⁴

Affiliations

¹ Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
² School of Clinical Medicine, Wannan Medical College, Wuhu 241002, China.
³ Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
⁴ Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.; Beijing Children's Hospital, Capital Medical University, China National Clinical Research Center of Respiratory Diseases, Beijing 100045, China. Electronic address: dingsg@ahmu.edu.cn.

PMID: 40651693
DOI: 10.1016/j.lfs.2025.123849

Abstract

Background: In recent years, it has been found that Th1 inflammation characterized by elevated levels of IFN-γ can be observed in the airways of patients with severe asthma, accompanied by polarization of M1 macrophages. However, the specific pathogenic role of M1 macrophages and their intrinsic regulatory factors in the development of asthma is still unclear.

Objective: We sought to investigate whether CXCL10 regulates M1 macrophage polarization through Sirt3.

Methods: Collecting peripheral blood samples from asthmatic children, ELISA was used to detect the levels of CXCL9, CXCL10, and CXCL11, and Western blot analyses was used to detect of the levels of Sirt3. We constructed an asthma mouse model and observed changes in macrophage polarization and Sirt3 by neutralizing CXCL10 or injecting CXCR antagonist AMG487. In addition, the effect of CXCL10 on Sirt3 mediated macrophage polarization was elucidated through in vitro experiments. The effect of M1 macrophage polarization on airway epithelial cells was investigated by co-culturing with conditioned medium.

Results: Clinical investigations showed that CXCL10 was highly expressed in peripheral blood of children with asthma, and was associated with impaired lung function (FEV1/FVC). Sirt3 expression in peripheral blood mononuclear cell was decreased. CXCL10 was found to the development of disease by promoting the M1 polarization of macrophages. Mechanistically, Sirt3 overexpression improved CXCL10-induced macrophage polarization.

Conclusions: CXCL10 promotes M1 macrophage polarization by inhibiting Sirt3, which plays an important role in the development of asthma.

Keywords: Asthma; CXCL10; Macrophage; Sirt3.