Avail Biomedical Research Institute, Basel, Switzerland.
Mucosal Immunol. 2012 Mar;5(2):140-9. doi: 10.1038/mi.2011.60. Epub 2011 Dec 21.
Fibrocytes contribute to the fibrotic changes most frequently observed in forms of asthma where inflammation is driven by T helper type 2 (Th2) cells. The mechanisms that regulate the profibrotic function of asthmatic fibrocytes are largely unknown. We isolated circulating fibrocytes from patients with allergen-exacerbated asthma, who showed the presence of fibrocytes, together with elevated concentrations of interleukin (IL)-4 and IL-13 and slightly increased concentrations of the Th17 cell-derived IL-17A, in induced sputum. Fibrocytes stimulated with IL-4 and IL-13 produced high levels of collagenous and non-collagenous matrix components and low levels of proinflammatory cytokines. Conversely, fibrocytes stimulated with IL-17A proliferated and released proinflammatory factors that may promote neutrophil recruitment and airway hyperresponsiveness. IL-17A also indirectly increased α-smooth muscle actin but not collagen expression in fibrocytes. Thus, fibrocytes may proliferate and express a predominant profibrotic or proinflammatory phenotype in asthmatic airways depending on the local concentrations of Th2- and Th17-derived cytokines.
成纤维细胞有助于哮喘的纤维化改变，这些改变通常发生在 Th2 细胞驱动的炎症形式中。调节哮喘成纤维细胞的成纤维功能的机制在很大程度上尚不清楚。我们从过敏原加重的哮喘患者中分离出循环成纤维细胞，这些患者的诱导痰中存在成纤维细胞，同时伴有白细胞介素（IL）-4 和 IL-13 浓度升高，Th17 细胞衍生的 IL-17A 浓度略有升高。IL-4 和 IL-13 刺激的成纤维细胞产生高水平的胶原和非胶原基质成分，以及低水平的促炎细胞因子。相反，IL-17A 刺激的成纤维细胞增殖并释放促炎因子，可能促进中性粒细胞募集和气道高反应性。IL-17A 还间接增加了成纤维细胞中的α-平滑肌肌动蛋白，但不增加胶原蛋白的表达。因此，成纤维细胞可能在哮喘气道中增殖并表达主要的成纤维或促炎表型，这取决于 Th2 和 Th17 衍生细胞因子的局部浓度。
