Galectin-9 modulates the Th1/Th2 balance to improve bronchial asthma

Bronchial asthma (BA) is a global chronic heterogeneous inflammatory disease. Galectin-9 (Gal-9) plays a significant role in inflammation and immunomodulation-related diseases, and both BA and Gal-9 are closely associated with the balance of helper T cells (Th1/Th2). This study aimed to investigate the potential mechanism by which Gal-9 ameliorates BA through modulating the Th1/Th2 balance.

Firstly, rat models of BA were established with two different degrees of airway challenge (three and six inhalation; n = 6 per group), to assess tissue damage and biomarker changes. Then, adenovirus containing Gal-9-specific expression silencing (sh-Gal-9) and interleukin 4 overexpressing adenovirus (oe-IL-4) were injected into a rat BA model (n = 6 per group), respectively, to examine lung tissue damage, inflammatory response, and Th1/Th2 cell ratio. Data were analyzed by ANOVA followed by Tukey's post hoc test.

A series of analyses showed that Gal-9 was highly expressed in the BA models (p < 0.01), accompanied by a Th2-biased Th1/Th2 imbalance. The imbalance and Gal-9 expression were exacerbated with increased excitation (p < 0.01). These effects were reversed by sh-Gal-9 injection, which restored a Th1-dominant balance (p < 0.01), and were counteracted by additional oe-IL-4 administration.

Inhibition of Gal-9 restores Th1/Th2 balance and reduces inflammation in BA, suggesting Gal-9 as a potential therapeutic target for asthma treatment.