Segawa S, Goto D, Iizuka A, Kaneko S, Yokosawa M, Kondo Y, Matsumoto I, Sumida T
Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Clin Exp Immunol. 2016 Sep;185(3):348-60. doi: 10.1111/cei.12802. Epub 2016 Aug 2.
Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with poor prognosis and high mortality. However, the pathogenesis of IP remains to be elucidated. The aim of this study was to clarify the role of pulmonary γδT cells in IP. In wild-type (WT) mice exposed to bleomycin, pulmonary γδT cells were expanded and produced large amounts of interferon (IFN)-γ and interleukin (IL)-17A. Histological and biochemical analyses showed that bleomycin-induced IP was more severe in T cell receptor (TCR-δ-deficient (TCRδ(-/-) ) mice than WT mice. In TCRδ(-/-) mice, pulmonary IL-17A(+) CD4(+) Τ cells expanded at days 7 and 14 after bleomycin exposure. In TCRδ(-/-) mice infused with γδT cells from WT mice, the number of pulmonary IL-17A(+) CD4(+) T cells was lower than in TCRδ(-/-) mice. The examination of IL-17A(-/-) TCRδ(-/-) mice indicated that γδT cells suppressed pulmonary fibrosis through the suppression of IL-17A(+) CD4(+) T cells. The differentiation of T helper (Th)17 cells was determined in vitro, and CD4(+) cells isolated from TCRδ(-/-) mice showed normal differentiation of Th17 cells compared with WT mice. Th17 cell differentiation was suppressed in the presence of IFN-γ producing γδT cells in vitro. Pulmonary fibrosis was attenuated by IFN-γ-producing γδT cells through the suppression of pulmonary IL-17A(+) CD4(+) T cells. These results suggested that pulmonary γδT cells seem to play a regulatory role in the development of bleomycin-induced IP mouse model via the suppression of IL-17A production.
间质性肺炎（IP）是一种慢性进行性间质性肺疾病，预后较差且死亡率高。然而，IP的发病机制仍有待阐明。本研究的目的是明确肺γδT细胞在IP中的作用。在暴露于博来霉素的野生型（WT）小鼠中，肺γδT细胞扩增并产生大量干扰素（IFN）-γ和白细胞介素（IL）-17A。组织学和生化分析表明，博来霉素诱导的IP在T细胞受体（TCR）δ缺陷（TCRδ（-/-））小鼠中比WT小鼠更严重。在TCRδ（-/-）小鼠中，博来霉素暴露后第7天和第14天肺IL-17A（+）CD4（+）T细胞扩增。在输注来自WT小鼠γδT细胞的TCRδ（-/-）小鼠中，肺IL-17A（+）CD4（+）T细胞数量低于TCRδ（-/-）小鼠。对IL-17A（-/-）TCRδ（-/-）小鼠的检查表明，γδT细胞通过抑制IL-17A（+）CD4（+）T细胞来抑制肺纤维化。体外测定辅助性T（Th）17细胞的分化，与WT小鼠相比，从TCRδ（-/-）小鼠分离的CD4（+）细胞显示Th17细胞正常分化。在体外存在产生IFN-γ的γδT细胞的情况下，Th17细胞分化受到抑制。产生IFN-γ的γδT细胞通过抑制肺IL-17A（+）CD4（+）T细胞减轻肺纤维化。这些结果表明，肺γδT细胞似乎通过抑制IL-17A的产生在博来霉素诱导的IP小鼠模型的发展中发挥调节作用。
