IL-17A⁺GM-CSF⁺ Neutrophils Are the Major Infiltrating Cells in Interstitial Lung Disease in an Autoimmune Arthritis Model.

ABSTRACT:

Objective

To gain a better understanding of the pathogenesis of autoimmune arthritis-associated interstitial lung disease (ILD), we sought to identify the characteristics of lung-infiltrating cells in SKG mice with ILD.

Methods

We injected curdlan in SKG mice at 8?weeks of age, and identified the presence of ILD by PET-MRI at 20?weeks post-injection and histological analysis at 22?weeks post-injection. Lung-infiltrating cells were examined by flow cytometry. Analysis of serum cytokines by the Luminex multiplex cytokine assay was performed at 14 and 22?weeks post-injection, and cytokine profiles before and after the development of ILD were compared. Opal multiplexed immunofluorescent staining of lung tissue was also performed.

Results

At 20?weeks post-injection, curdlan-treated SKG mice developed not only arthritis but also lung inflammation combined with fibrosis, which was identified by PET-MRI and histological analysis. The majority of inflammatory cells that accumulated in the lungs of curdlan-treated SKG mice were CD11b⁺Gr1⁺ neutrophils, which co-express IL-17A and GM-CSF, rather than TNF-?. Compared with 14?weeks post-injection, serum levels of GM-CSF, MCP1, IL-17A, IL-23, TSLP, and soluble IL-7R? had increased at 22?weeks post-injection, whereas those of IFN-?, IL-22, IL-6, and TNF-? remained unchanged. Furthermore, IL-23, CXCL5, IL-17A, and GM-CSF, but not TNF-?, were observed in immunofluorescent-stained lung tissue.

Conclusion

We found that IL-17A⁺GM-CSF⁺ neutrophils represented the major inflammatory cells in the lungs of curdlan-treated SKG mice. In addition, GM-CSF and IL-17A appear to play a more important role than TNF-? in ILD development.

SUBMITTER: Kwon OC 

PROVIDER: S-EPMC6036238 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature