RRC ID 19216
Author Ishikawa K, Toyama-Sorimachi N, Nakada K, Morimoto M, Imanishi H, Yoshizaki M, Sasawatari S, Niikura M, Takenaga K, Yonekawa H, Hayashi J.
Title The innate immune system in host mice targets cells with allogenic mitochondrial DNA.
Journal J. Exp. Med.
Abstract Mitochondrial DNA (mtDNA) has been proposed to be involved in respiratory function, and mtDNA mutations have been associated with aging, tumors, and various disorders, but the effects of mtDNA imported into transplants from different individuals or aged subjects have been unclear. We examined this issue by generating trans-mitochondrial tumor cells and embryonic stem cells that shared the syngenic C57BL/6 (B6) strain-derived nuclear DNA background but possessed mtDNA derived from allogenic mouse strains. We demonstrate that transplants with mtDNA from the NZB/B1NJ strain were rejected from the host B6 mice, not by the acquired immune system but by the innate immune system. This rejection was caused partly by NK cells and involved a MyD88-dependent pathway. These results introduce novel roles of mtDNA and innate immunity in tumor immunology and transplantation medicine.
Volume 207(11)
Pages 2297-305
Published 2010-10-25
DOI 10.1084/jem.20092296
PII jem.20092296
PMID 20937705
PMC PMC2964578
MeSH Aging / genetics Aging / immunology Animals Carcinoma, Lewis Lung / genetics Carcinoma, Lewis Lung / immunology* Cell Line, Tumor DNA, Mitochondrial / genetics DNA, Mitochondrial / immunology* Embryonic Stem Cells / immunology* Graft Rejection / genetics Graft Rejection / immunology* Immunity, Innate / physiology* Killer Cells, Natural / immunology Mice Mice, Inbred NZB Mutation Myeloid Differentiation Factor 88 / genetics Myeloid Differentiation Factor 88 / immunology Neoplasm Transplantation Stem Cell Transplantation* Transplantation, Homologous
IF 10.79
Times Cited 20
Human and Animal Cells B6G-2 (AES0003)