Keratin mediates the recognition of apoptotic and necrotic cells through dendritic cell receptor DEC205/CD205

被引：33

作者：

Cao, Longxing ^{[1
,2
]}

Chang, Haishuang ^{[1
]}

Shi, Xiangyi ^{[1
]}

Peng, Chao ^{[1
]}

He, Yongning ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol,Natl Ctr Prot Sci,Shanghai, Shanghai 201210, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2016年 / 113卷 / 47期

基金：

中国国家自然科学基金;

关键词：

DEC205/CD205; keratin; dead cell recognition; mannose receptor family; cell death; CLUMPING FACTOR-B; INTERMEDIATE-FILAMENTS; IMMUNE-RESPONSES; MANNOSE RECEPTOR; IN-VIVO; EXTRACELLULAR ACIDOSIS; MONOCLONAL-ANTIBODY; CARCINOMA-CELLS; CYTOKERATIN; SURFACE;

D O I：

10.1073/pnas.1609331113

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：13438 / 13443

页数：6

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