IL-17 contributes to the pathogenesis of obliterative bronchiolitis via regulation of M1 macrophages polarization in murine heterotopic trachea transplantation models

- Deficiency of IL-17 attenuated the pathology of murine HTT allografts.
- Deficiency of IL-17 contributed to M2 while inhibited M1 macrophages polarization in vivo and in vitro.
- Deficiency of IL-17 suppressed LPS induced M1 polarization and function through STAT signaling pathway.

Acute allograft rejection is a principal conundrum in lung obliterative bronchiolitis (OB). Monocytes/macrophages infiltration has been proved to be the main reason for acute rejection. IL-17 contributes to the recruitment and function of macrophages. However, the mechanism of IL-17 underlying OB progression remains elusive. In the present study, we showed that the deficiency of IL-17 attenuated the pathology of murine heterotopic trachea allografts. Compared to WT recipients, IL-17−/− mice displayed higher frequency of CD206 + cells and lower ratio of CD86 + cells among F4/80 + macrophages in allografts and spleens on day 7 post heterotopic trachea transplantation. Moreover, mRNA levels of pro-inflammatory cytokines including IL-6, TNF-α, and IL-1β decreased in allografts of IL-17−/− recipients, but these of MRC1 and Arg-1 increased in comparison with WT. IL-17 deficiency can inhibit LPS induced M1 while promote IL-4 induced M2 polarization of bone marrow-derived macrophages. Further data demonstrated that the deficiency of IL-17 suppressed the lipopolysaccharide-induced M1 polarization and function through prevention of phosphorylation of both STAT3 and STAT5. Therefore, IL-17 contributes to OB pathogenesis through regulating macrophages function, thereby it may unravel part of the complexity of IL-17 in OB and enhance future therapeutic development.