Abstract：
Interleukin (IL)-23 is implicated in the pathogenesis of several inflammatory diseases and is usually linked with helper T cell (Th17) biology. However, there is some data linking IL-23 with innate immune biology in such diseases. We therefore examined the effects of IL-23p19 genetic deletion and/or neutralization on in vitro macrophage activation and in an innate immune-driven peritonitis model. We report that endogenous IL-23 was required for maximal macrophage activation by zymosan as determined by pro-inflammatory cytokine production, including a dramatic upregulation of granulocyte-colony stimulating factor (G-CSF). Furthermore, both IL-23p19 genetic deletion and neutralization in zymosan-induced peritonitis (ZIP) led to a specific reduction in the neutrophil numbers, as well as a reduction in the G-CSF levels in exudate fluids. We conclude that endogenous IL-23 can contribute significantly to macrophage activation during an inflammatory response, mostly likely via an autocrine/paracrine mechanism; of note, endogenous IL-23 can directly up-regulate macrophage G-CSF expression, which in turn is likely to contribute to the regulation of IL-23-dependent neutrophil number and function during an inflammatory response, with potential significance for IL-23 targeting particularly in neutrophil-associated inflammatory diseases.
摘要：
白细胞介素（IL）-23与几种炎性疾病的发病机理有关，通常与辅助T细胞（Th17）生物学有关。然而,有一些数据将IL-23与此类疾病的先天免疫生物学联系起来。因此，我们检查了IL-23p19基因缺失和/或中和对体外巨噬细胞活化和先天免疫驱动的腹膜炎模型的影响。我们报告说，内源性IL-23是酵母聚糖对巨噬细胞的最大激活所必需的，这是由促炎细胞因子的产生所决定的。包括粒细胞集落刺激因子（G-CSF）的急剧上调。此外，在酵母聚糖诱导的腹膜炎（ZIP）中，IL-23p19基因缺失和中和导致中性粒细胞数量的特定减少，以及渗出液中G-CSF水平的降低。我们得出结论，内源性IL-23可以在炎症反应期间显著促进巨噬细胞活化，主要可能是通过自分泌/旁分泌机制；值得注意的是，内源性IL-23可直接上调巨噬细胞G-CSF的表达,这反过来可能有助于在炎症反应期间调节IL-23依赖性中性粒细胞的数量和功能，特别是在中性粒细胞相关的炎性疾病中，IL-23靶向具有潜在意义。
