Evasion of myofibroblasts from immune surveillance: a mechanism for tissue fibrosis.
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.
Wallach-Dayan
Shulamit B
SB
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary Medicine Hadassah, Hebrew University Medical Center, Jerusalem 91120, Israel. wallach-dayan@hadassah.org.il
Golan-Gerstl
Regina
R
Breuer
Raphael
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics; D005347:Fibroblasts / Q000276:immunology*; D005355:Fibrosis; D007157:Immunologic Surveillance; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D032446:Myoblasts / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D000199:Actins; D053222:Fas Ligand Protein; D019014:fas Receptor; D003094:Collagen