A role for calreticulin in the pathogenesis of rheumatoid arthritis

Calreticulin (CRT) plays a role in the clearance of dying cells and has been implicated in autoimmunity. Recent evidence indicates that cell surface CRT (csCRT) acts as a signal transducing receptor for the rheumatoid arthritis (RA) shared epitope (SE). The SE binding site on CRT has been mapped to...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2010-10, Vol.1209 (1), p.91-98
Main Authors: Holoshitz, Joseph, De Almeida, Denise E., Ling, Song
Format: Article
Language:English
Subjects:
Animals
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - physiopathology
Binding sites
calreticulin
Calreticulin - physiology
CD8 Antigens - immunology
Cell Differentiation
Epitopes - immunology
Humans
Medical research
Mice
nitric oxide
Rheumatoid arthritis
shared epitope
T-Lymphocytes, Regulatory - cytology
T-Lymphocytes, Regulatory - immunology
Th17
Treg
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Summary:Calreticulin (CRT) plays a role in the clearance of dying cells and has been implicated in autoimmunity. Recent evidence indicates that cell surface CRT (csCRT) acts as a signal transducing receptor for the rheumatoid arthritis (RA) shared epitope (SE). The SE binding site on CRT has been mapped to amino acid residues 217–223 in the P‐domain. Upon interaction with dendritic cells (DCs), the SE activates potent immune regulatory events. In CD8α+ DCs, which express higher abundance of csCRT, the SE inhibits the tolerogenic enzyme indoleamine 2,3 dioxygenase with resultant inhibition of regulatory T (Treg) cell differentiation. In CD8α− DCs, the SE ligand increases secretion of IL‐6 and IL‐23 and facilitates generation of Th17 cells, a T cell subset known to play a role in autoimmunity. On the basis of these recent findings, we discuss the possibility that the csCRT may play a pathogenic role in RA by transducing SE‐activated Th17‐polarizing signals.
ISSN:0077-8923
1749-6632
DOI:10.1111/j.1749-6632.2010.05745.x