BACKGROUND

The role of inducible costimulator (ICOS) signaling in chronic obstructive pulmonary disease (COPD) has not been fully elucidated.

METHODS

We compared the percentages of ICOS T cells and ICOS regulatory T (Treg) cells in CD4 T cells and CD4CD25FOXP3 Tregs, respectively, in the peripheral blood of smokers with or without COPD to those in healthy controls. We further characterized their phenotypes using flow cytometry. To investigate the influence of ICOS signaling on C-X-C motif chemokine receptor 3 (CXCR3) expression in COPD, we evaluated the expression levels of ICOS and CXCR3 in vivo and in vitro.

RESULTS

ICOS expression was elevated on peripheral CD4 T cells and CD4 Tregs of COPD patients, which positively correlated with the severity of lung function impairment in patients with stable COPD (SCOPD), but not in patients with acute exacerbation of COPD (AECOPD). ICOSCD4 Tregs in patients with SCOPD expressed higher levels of coinhibitors, programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT), than ICOSCD4 Tregs, whereas ICOSCD4 T cells mostly exhibited a central memory (CD45RACCR7) or effector memory (CD45RACCR7) phenotype, ensuring their superior potential to respond potently and quickly to pathogen invasion. Furthermore, increased percentages of CXCR3CD4 T cells and CXCR3CD4 Tregs were observed in the peripheral blood of patients with SCOPD, and the expression level of CXCR3 was higher in ICOSCD4 T cells than in ICOSCD4 T cells. The percentage of CXCR3CD4 T cells was even higher in the bronchoalveolar lavage fluid than in matched peripheral blood in SCOPD group. Lastly, in vitro experiments showed that ICOS induced CXCR3 expression on CD4 T cells.

CONCLUSIONS

ICOS signaling is upregulated in COPD, which induces CXCR3 expression. This may contribute to increased numbers of CXCR3 Th1 cells in the lungs of patients with COPD, causing inflammation and tissue damage.