Billions of cells are turned over every day in human body through apoptosis or killed by pathological infections and inflammation. It is critical for the immune system to clean dead cells efficiently in order to maintain homeostasis and avoid autoimmune diseases. This process is usually carried out by the immune cells such as dendritic cells and macrophages through recognizing the specific markers on dead cells.
DEC205 (CD205) is a typical surface receptor of dendritic cells, and has been widely used as a target for vaccine generation in immune therapies. It has been shown that DEC205 undergoes a dramatic conformational change between acidic and basic environments, and it only recognizes dead cells specifically at acidic pH. However, it is still unclear how DEC205 recognizes dead cells, plus the cellular ligand of DEC205 has remained unknown since 1995.
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 (SIBCB), Shanghai Institutes for Biological Sciences, CAS, utilize a number of biochemical and biophysical methods such as mass spectrometry, confocal microscopy, flow cytometry, etc., to look for the natural ligand of human DEC205. And eventually they find that keratins are the cellular ligands of DEC205, and DEC205 only recognizes keratins 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 are exposed after cell death and then recognized by immune receptor DEC205 in acid conditions, therefore function as dead cell markers.
Moreover, it has been realized for a long time that keratins are correlated with tumorigenesis, and keratins have been used as diagnostic markers for various tumors. Therefore 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 of China and the National Natural Science Foundation of China.
Keratin mediates dead cell recognition through DEC205.
(Image Provided by Prof. HE Yongning's Lab)
HE Yongning, Ph.D.
Institute of Biochemistry and Cell Biology,
Shanghai Institutes for Biological Sciences,
Chinese Academy of Sciences