Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates interstitial lung disease in SKG mice.

Abstract

BACKGROUND:

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a sometimes life-threatening complication in RA patients. SKG mice develop not only arthritis but also an ILD resembling RA-ILD. We previously reported that tofacitinib, a JAK inhibitor, facilitates the expansion of myeloid-derived suppressor cells (MDSCs) and ameliorates arthritis in SKG mice. The aim of this study was to elucidate the effect of tofacitinib on the ILD in SKG mice.

METHODS:

We assessed the effect of tofacitinib on the zymosan (Zym)-induced ILD in SKG mice histologically and examined the cells infiltrating the lung by flow cytometry. The effects of lung MDSCs on T cell proliferation and Th17 cell differentiation were assessed in vitro. We also evaluated the effects of tofacitinib on MDSCs and dendritic cells in vitro.

RESULTS:

Tofacitinib significantly suppressed the progression of ILD compared to the control SKG mice. The MDSCs were increased, while Th17 cells, group 1 innate lymphoid cells (ILC1s), and GM-CSF+ILCs were decreased in the lungs of tofacitinib-treated mice. MDSCs isolated from the inflamed lungs suppressed T cell proliferation and Th17 cell differentiation in vitro. Tofacitinib promoted MDSC expansion and suppressed bone marrow-derived dendritic cell (BMDC) differentiation in vitro.

CONCLUSION:

Tofacitinib facilitates the expansion of MDSCs in the lung and ameliorates ILD in SKG mice.

• Authors: Sho Sendo, Jun Saegusa, Hirotaka Yamada, Keisuke Nishimura, Akio Morinobu
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 21 Issue 1 Pg. 184 (08 06 2019) ISSN: 1478-6362 [Electronic] England
• PMID: 31387650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperidines
• Protein Kinase Inhibitors
• Pyrimidines
• Pyrroles
• tofacitinib

Topics

• Animals
• Cell Differentiation
• Cell Proliferation
• Dendritic Cells (immunology, pathology)
• Disease Models, Animal
• Immunity, Innate
• Lung Diseases, Interstitial (drug therapy, metabolism, pathology)
• Male
• Mice
• Piperidines (pharmacology)
• Protein Kinase Inhibitors (pharmacology)
• Pyrimidines (pharmacology)
• Pyrroles (pharmacology)
• Th17 Cells (immunology)