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

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.