Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205.
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.
State Key Laboratory of Molecular Biology, National Center for Protein Science, Shanghai Science Research Center, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
Longxing
L
Cao
State Key Laboratory of Molecular Biology, National Center for Protein Science, Shanghai Science Research Center, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China.
Haishuang
H
Chang
State Key Laboratory of Molecular Biology, National Center for Protein Science, Shanghai Science Research Center, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China.
Xiangyi
X
Shi
State Key Laboratory of Molecular Biology, National Center for Protein Science, Shanghai Science Research Center, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China.
Chao
C
Peng
State Key Laboratory of Molecular Biology, National Center for Protein Science, Shanghai Science Research Center, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China; he@sibcb.ac.cn.
Yongning
Y
He
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D017209:Apoptosis; D003713:Dendritic Cells / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019169:Jurkat Cells; D007633:Keratins / Q000737:chemistry / Q000378:metabolism*; D037181:Lectins, C-Type / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000737:chemistry / Q000378:metabolism*; D009336:Necrosis; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*
D015703:Antigens, CD; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D008024:Ligands; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D007633:Keratins; D006026:Glycoside Hydrolases
DEC205/CD205; cell death; dead cell recognition; keratin; mannose receptor family