Wallach-Dayan Shulamit B, Golan-Gerstl Regina, Breuer Raphael
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine Hadassah, Hebrew University Medical Center, Jerusalem 91120, Israel.
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20460-5. doi: 10.1073/pnas.0705582104. Epub 2007 Dec 11.
Tissue fibrosis evolving from impaired tissue remodeling after injury is characterized by myofibroblast accumulation. We propose that during the development of fibrosis myofibroblasts acquire an immune-privileged cell phenotype, allowing their uninterrupted accumulation. Using the murine model of bleomycin-induced lung fibrosis in mice, we show that myofibroblasts that accumulate in lungs with fibrosis, but not in normal lungs, kill Fas(+) lymphocytes, resist Fas-induced apoptosis, and survive longer when grafted into allogeneic mice. In contrast, bleomycin-treated FasLigand (FasL)-deficient (gld) chimeric mice did not accumulate myofibroblasts or collagen in their lungs, and their FasL(-) myofibroblasts did not survive after alloengraftment. This finding indicates that myofibroblasts possess Fas/FasL-pathway-dependent characteristics that allow them to escape from immune surveillance and resulting organ fibrosis.
损伤后组织重塑受损引发的组织纤维化，其特征为肌成纤维细胞的积累。我们提出，在纤维化发展过程中，肌成纤维细胞获得了免疫豁免细胞表型，从而使其能够持续积累。利用博来霉素诱导的小鼠肺纤维化模型，我们发现，在纤维化肺中积累的肌成纤维细胞，而非正常肺中的肌成纤维细胞，能够杀死Fas(+)淋巴细胞，抵抗Fas诱导的凋亡，并且在移植到同种异体小鼠中时存活时间更长。相比之下，经博来霉素处理的Fas配体（FasL）缺陷（gld）嵌合小鼠的肺中未积累肌成纤维细胞或胶原蛋白，且其FasL(-)肌成纤维细胞在同种异体移植后无法存活。这一发现表明，肌成纤维细胞具有依赖Fas/FasL途径的特性，使其能够逃避免疫监视并导致器官纤维化。
