Keratins are endogenous ligands of DEC205

In November 7, 2016, the United States Academy of Sciences (PNAS) published a research result titled “Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205” online and it was completed by He Yongning research group at the Chinese Academy of Sciences Shanghai Institute of life science biochemistry and cell biology Institute using recombinant human proteins, which discloses the molecular mechanism of immunoreceptor DEC205 / CD205 recognizing dead cells by binding to cytokeratin.

A large number of cells die in the human body every day. The identification of dead cells and clean-up is indispensable to maintain the body's homeostasis and avoid autoimmune diseases and is also an important function of the immune system. It is usually completed by dendritic cells, macrophages and other phagocytic cells. Phagocytic cells need to recognize dead cells through their surface receptor molecules. DEC205 (CD205) is one of the main markers and endocytotic receptors of dendritic cells and is widely used in immunotherapy. But its function is very limited understanding. Since the receptor was found in 1995, the cell ligand has not been found. In a previous study, the team found that the extracellular portion of DEC205 exhibited different conformations under acidic and basic conditions and that this conformational change was directly related to its function. DEC205 specifically recognizes apoptotic necrotic cells only under acidic conditions, thus revealing its physiological function as a dying cell receptor (PNAS, 2015). However, how DEC205 recognizes dead cells is still unclear.

In this work, on the basis of previous results, Cao Longxing and other researchers looked for human DEC205 on the cell ligands through a series of biochemical and biophysical experiments. As a result, it was found that keratins are endogenous ligands of DEC205. Further experiments have shown that the human DEC205 molecule can specifically recognize the C-terminal domain of keratin by its N-terminal domain under acidic conditions. Keratin is an important component of the cytoskeleton and usually can form fibrous intermediate filaments involved in the maintenance of cell morphology and mechanical properties, but other physiological role of keratin is not very clear. This work shows that keratin not only plays an important role in maintaining the cell and tissue structure, but also as a marker of cell death and is recognized by the immune system and mediates an acid-base-dependent death cell recognition pathway. In addition, keratin and tumor also exist between the close contact and is used for clinical diagnosis of a variety of tumors. Therefore, the finding of DEC205 as a keratin receptor provides a new way of thinking for diagnosis and treatment of cancer and related diseases. Flarebio offers good-quality recombinant proteins such as recombinant ITGB5 at competitive prices.