Billions of cells are turned over every day in human body through apoptosis or killed by pathological infections and inflammation. To maintain homeostasis and avoid various diseases, dead cells have to be cleaned by phagocytes such as dendritic cells and macrophages through specific markers on cell surface.
DEC205 (CD205) is an endocytotic receptor and also a typical marker of dendritic cells, and has been widely used as a receptor target for vaccine generation in immune therapies. It has been shown that DEC205 undergoes a dramatic conformational change between acidic and basic environments, and the conformational change is correlated with its ligand binding and release. DEC205 only recognizes dead cells specifically at acidic pH. However, the cellular ligand of DEC205 has remained unknown since 1995, it is still unclear how DEC205 recognizes dead cells in acidic environments.
In a paper published online on November 7, 2016 by the Proceedings of the National Academy of Sciences USA, scientists from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, find that keratins are the cellular ligands of DEC205. They also found that DEC205 recognizes the C-terminal domains of keratins through its N-terminal domains, and this recognition only happens in acidic, rather than basic, environments. It is well known that keratins are structural proteins forming intermediate filaments and provide mechanical support for cells and tissues, but their physiological roles other than cytoskeleton have not been fully understood. The results in this paper suggest that keratins also function as markers of apoptotic and necrotic cells and mediate a pH-dependent pathway for the immune recognition of dead cells. Moreover, since keratins have been used as diagnostic markers for various tumors, the finding of DEC205 as a receptor for keratins may provide insights for the therapeutic strategies against tumors and other related diseases.
This research is supported by the grants from the Chinese Academy of Sciences, the Ministry of Science and Technology and the National Natural Science Foundation of China.
CONTACT:
HE Yongning, Ph.D.
Principal Investigator
Institute of Biochemistry and Cell Biology,
Shanghai Institutes for Biological Sciences,
Chinese Academy of Sciences
Shanghai, China
E-mail: he@sibcb.ac.cn
Keratin mediates dead cell recognition through DEC205
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