Department of Respiratory Diseases, Changhai Hospital, the Second Military Medical University, Shanghai, PR China.
Clin Immunol. 2012 Mar;142(3):269-79. doi: 10.1016/j.clim.2011.11.001. Epub 2011 Nov 20.
The mechanisms by which mast cells (MCs) regulate immune responses are still largely unknown. Here, we showed that MCs induced interleukin (IL)-10 producing T cells to regulate inflammatory responses. To gain insight into the molecules involved, we set up an in vitro system in which lipopolysaccharide (LPS) stimulated MCs and CD4(+) T cells were co-cultured. Induction of IL-10 producing regulatory T cells mainly relied on the inducible costimulator ligand (ICOSL)/ICOS axis. MCs stimulated with LPS for more than 6 weeks upregulated ICOSL expression, while icosl(-/-) BMMCs failed to induce IL-10 producing T cells. The LPS effect was mediated through NF-κB activation via the TLR4 signaling pathway. Ex vivo analysis of bronchoalveolar lavage fluid from mice with LPS-mediated pneumonia revealed ICOSL(+) MCs and IL-10 producing T cell induction. Additionally, adaptive transfer of ICOSL(+) BMMCs attenuated LPS-mediated inflammation in MC-deficient mice. This study provided new evidence for the regulatory role of MCs.
肥大细胞（MCs）调节免疫反应的机制在很大程度上仍然未知。在这里，我们表明 MCs 诱导白细胞介素（IL）-10 产生 T 细胞来调节炎症反应。为了深入了解所涉及的分子，我们建立了一个体外系统，其中脂多糖（LPS）刺激 MCs 并共培养 CD4(+) T 细胞。诱导产生 IL-10 的调节性 T 细胞主要依赖于诱导共刺激配体（ICOSL）/ICOS 轴。用 LPS 刺激超过 6 周的 MCs 上调 ICOSL 表达，而 icosl(-/-) BMMCs 未能诱导 IL-10 产生 T 细胞。LPS 的作用是通过 TLR4 信号通路通过 NF-κB 激活来介导的。来自 LPS 介导性肺炎小鼠的支气管肺泡灌洗液的体外分析显示 ICOSL(+) MCs 和 IL-10 产生 T 细胞的诱导。此外，ICOSL(+) BMMCs 的适应性转移减轻了 MC 缺陷小鼠中 LPS 介导的炎症。这项研究为 MCs 的调节作用提供了新的证据。
