Allard Jenna B, Poynter Matthew E, Marr Kieren A, Cohn Lauren, Rincon Mercedes, Whittaker Laurie A
Vermont Lung Center, Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
J Immunol. 2006 Oct 15;177(8):5186-94. doi: 10.4049/jimmunol.177.8.5186.
Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20-40% of CF patients and are of unclear clinical significance. In this study, we demonstrate that CF transmembrane conductance regulator (CFTR)-deficient (CFTR knockout, Cftr(tm1Unc-)TgN(fatty acid-binding protein)CFTR) and mutant (DeltaF508) mice develop profound lung inflammation in response to Aspergillus fumigatus hyphal Ag exposure. CFTR-deficient mice also develop an enhanced Th2 inflammatory response to A. fumigatus, characterized by elevated IL-4 in the lung and IgE and IgG1 in serum. In contrast, CFTR deficiency does not promote a Th1 immune response. Furthermore, we demonstrate that CD4+ T cells from naive CFTR-deficient mice produce higher levels of IL-4 in response to TCR ligation than wild-type CD4+ T cells. The Th2 bias of CD4+ T cells in the absence of functional CFTR correlates with elevated nuclear levels of NFAT. Thus, CFTR is important to maintain the Th1/Th2 balance in CD4+ T cells.
囊性纤维化（CF）肺部疾病的特征是持续性气道炎症和气道感染，最终导致呼吸衰竭。曲霉菌属存在于20%-40%的CF患者气道中，其临床意义尚不清楚。在本研究中，我们证明囊性纤维化跨膜传导调节因子（CFTR）缺陷型（CFTR基因敲除，Cftr(tm1Unc-)TgN(脂肪酸结合蛋白)CFTR）和突变型（ΔF508）小鼠在暴露于烟曲霉菌丝抗原后会发生严重的肺部炎症。CFTR缺陷型小鼠对烟曲霉还产生增强的Th2炎症反应，其特征是肺中IL-4水平升高以及血清中IgE和IgG1水平升高。相比之下，CFTR缺陷不会促进Th1免疫反应。此外，我们证明，与野生型CD4+T细胞相比，来自未接触过抗原的CFTR缺陷型小鼠的CD4+T细胞在TCR连接后产生更高水平的IL-4。在缺乏功能性CFTR的情况下，CD4+T细胞的Th2偏向与NFAT核水平升高相关。因此，CFTR对于维持CD4+T细胞中的Th1/Th2平衡很重要。
