Immunoregulation Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC.
Blood. 2012 Dec 6;120(24):4761-71. doi: 10.1182/blood-2012-04-424226. Epub 2012 Oct 15.
Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3- or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T(EM)), central memory T cells (T(CM)), and CCR6(+) CD4 T cells. More specifically, basophils promoted the emergence of IL-17(+)IFN-γ(-) and IL-17(+)IFN-γ(+), but not IL-17(-)IFN-γ(+) CD4 T cells in T(EM) and T(CM). Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in T(EM) involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H(2) and H(4) histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.
嗜碱性粒细胞是一种罕见的粒细胞群体，长期以来一直与 IgE 介导和 Th2 相关的过敏性疾病相关。然而，嗜碱性粒细胞在 Th17 和/或 Th1 疾病中的作用尚未被报道。在本研究中，我们报告嗜碱性粒细胞可在 Th17 相关的肺部和炎症性肠病的粘膜中被检测到，并在含有大量 IL-33 的发炎结肠中积聚。我们还证明循环嗜碱性粒细胞增加了记忆性 Th17 反应。相应地，IL-3 或 IL-33 激活的嗜碱性粒细胞在效应记忆性 T 细胞 (T(EM))、中央记忆性 T 细胞 (T(CM)) 和 CCR6(+) CD4 T 细胞中放大了 IL-17 的释放。更具体地说，嗜碱性粒细胞促进了 IL-17(+)IFN-γ(-)和 IL-17(+)IFN-γ(+)，但不是 IL-17(-)IFN-γ(+) CD4 T 细胞在 T(EM)和 T(CM)中的出现。机制分析表明，嗜碱性粒细胞在 T(EM)中增强 IL-17 产生的作用涉及 ERK1/2 信号通路，以非接触依赖性方式发生，并且部分通过组胺通过 H(2)和 H(4)组胺受体介导。本研究的结果揭示了嗜碱性粒细胞在增强记忆性 CD4 T 细胞中 Th17 和 Th17/Th1 细胞因子表达方面的一个以前未知的功能。由于嗜碱性粒细胞在发炎的炎症性肠病组织中积聚，我们提出这些细胞是慢性炎症性疾病中除 Th2 以外的关键参与者。
