期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：47
页码：13438-13443
DOI：10.1073/pnas.1609331113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceDEC205 (CD205) is an endocytotic receptor on dendritic cells that recognizes dead cells in a pH-dependent fashion and has been widely used for vaccine generation in immune therapies. However, the physiological ligand(s) of DEC205 has remained unknown for decades. Here we identify that keratins are the cellular ligands of human DEC205 and DEC205 recognizes keratins specifically at acidic pH. Keratins are structural proteins providing mechanical support for cells and tissues. Our results suggest that keratins act as markers of dead cells in acidic environments. Moreover, since keratins have been used as diagnostic markers for various tumors, the finding of DEC205 as a scavenging receptor of keratins may provide insights for the therapeutic strategies against tumors and other related diseases. Clearance of dead cells is critical for maintaining homeostasis and prevents autoimmunity and inflammation. When cells undergo apoptosis and necrosis, specific markers are exposed and recognized by the receptors on phagocytes. DEC205 (CD205) is an endocytotic receptor on dendritic cells with antigen presentation function and has been widely used in immune therapies for vaccine generation. It has been shown that human DEC205 recognizes apoptotic and necrotic cells in a pH-dependent fashion. However, the natural ligand(s) of DEC205 remains unknown. Here we find that keratins are the cellular ligands of human DEC205. DEC205 binds to keratins specifically at acidic, but not basic, pH through its N-terminal domains. Keratins form intermediate filaments and are important for maintaining the strength of cells and tissues. Our results suggest that keratins also function as cell markers of apoptotic and necrotic cells and mediate a pH-dependent pathway for the immune recognition of dead cells.
关键词：DEC205/CD205 ; keratin ; dead cell recognition ; mannose receptor family ; cell death
