Invariant Natural Killer T Cells Play a Role in Chemotaxis, Complement Activation and Mucus Production in a Mouse Model of Airway Hyperreactivity and Inflammation

CD1d-restricted invariant natural killer T (iNKT) cells play a critical role in the induction of airway hyperreactivity (AHR). After intranasal alpha-galactosylceramide (α-GalCer) administration, bronchoalveolar lavage fluid (BALF) proteins from mouse lung were resolved by two-dimensional differential gel electrophoresis (2D-DIGE), and identified by tandem mass spectroscopy. A lack of iNKT cells prevented the development of airway responses including AHR, neutrophilia and the production of the proinflammatory cytokines in lungs. Differentially abundant proteins in the BALF proteome of α-GalCer-treated wild type mice included lungkine (CXCL15), pulmonary surfactant-associated protein D (SFTPD), calcium-activated chloride channel regulator 1 (CLCA1), fragments of complement 3, chitinase 3-like proteins 1 (CH3LI) and 3 (CH3L3) and neutrophil gelatinase-associated lipocalin (NGAL). These proteins may contribute to iNKT regulated AHR via several mechanisms: altering leukocyte chemotaxis, increasing airway mucus production and possibly via complement activation.CD1d限制性不变自然杀伤T（iNKT）细胞在气道高反应性（AHR）的诱导中发挥关键作用。经鼻内给予α-半乳糖神经酰胺（α-GalCer）后，研究人员通过二维差异凝胶电泳（2D-DIGE）分离了小鼠肺部支气管肺泡灌洗液（BALF）中的蛋白质，并采用串联质谱（tandem mass spectroscopy）对其进行鉴定。iNKT细胞的缺失会阻断气道反应的发生发展，这类反应包括AHR、中性粒细胞增多以及肺部促炎细胞因子的产生。经α-GalCer处理的野生型小鼠的BALF蛋白质组中，差异丰度蛋白包括肺趋化因子（CXCL15）、肺表面活性物质相关蛋白D（SFTPD）、钙激活氯离子通道调节蛋白1（CLCA1）、补体3片段、几丁质酶3样蛋白1（CH3LI）与3（CH3L3），以及中性粒细胞明胶酶相关脂质运载蛋白（NGAL）。上述蛋白可能通过多种机制参与iNKT细胞调控的AHR：改变白细胞趋化行为、增加气道黏液生成，或通过补体激活途径发挥作用。