托法替尼促进髓源抑制细胞的扩增，并改善 SKG 小鼠的间质性肺病。
Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates interstitial lung disease in SKG mice.
机构信息
Department of Internal Medicine, Division of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Department of Endocrinology and Rheumatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan.
出版信息
Arthritis Res Ther. 2019 Aug 6;21(1):184. doi: 10.1186/s13075-019-1963-2.
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.
背景
类风湿关节炎相关间质性肺病（RA-ILD）是类风湿关节炎患者的一种有时危及生命的并发症。SKG 小鼠不仅会发生关节炎，还会发生类似于 RA-ILD 的间质性肺病。我们之前报道过，JAK 抑制剂托法替尼可促进髓系来源的抑制细胞（MDSCs）的扩增，并改善 SKG 小鼠的关节炎。本研究旨在阐明托法替尼对 SKG 小鼠间质性肺病的影响。
方法
我们通过组织学评估托法替尼对 SKG 小鼠酵母聚糖（Zym）诱导的间质性肺病的影响，并通过流式细胞术检查浸润肺部的细胞。体外评估肺 MDSC 对 T 细胞增殖和 Th17 细胞分化的影响。我们还评估了托法替尼对体外 MDSC 和树突状细胞的影响。
结果
与对照 SKG 小鼠相比，托法替尼显著抑制了间质性肺病的进展。在接受托法替尼治疗的小鼠肺部，MDSCs 增加，而 Th17 细胞、第 1 组先天淋巴细胞（ILC1）和 GM-CSF+ILC 减少。从发炎的肺部分离出的 MDSC 可在体外抑制 T 细胞增殖和 Th17 细胞分化。托法替尼促进 MDSC 扩增并抑制体外骨髓来源的树突状细胞（BMDC）分化。
结论
托法替尼促进肺部 MDSC 的扩增，并改善 SKG 小鼠的间质性肺病。
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