CD161 receptor participates in both impairing NK cell cytotoxicity and the response to glycans and vimentin in patients with rheumatoid arthritis.
We investigated the role of natural killer (NK) cells and CD161, their primary C-type-lectin-like receptor in rheumatoid arthritis (RA). Samples were compared with healthy donors (HD), dermatomyositic (DM), polymyositic (PM), and osteoarthritic (OA) patients. RA, PM, and DM NK cell cytotoxicities significantly decreased relative to the HD and OA NK cells (p<0.0001). These results correlated with an increased expression of NK cell inhibitory receptor CD161, in active disease RA patients. We demonstrated that NK cells are able to respond to mutated citrullinated vimentin (MCV), an RA-specific autoantigen, leading to increases in both PAD4 enzyme and CD161 mRNA expression. MGAT5 glycosidase involvement was detected in GlcNAc metabolism within the synoviocytes of RA patients. Our findings reveal a functional relationship between CD161 expression and NK cell cytotoxicity as well as reactivity to glycans and MCV, thus providing new insight into the pathogenesis of RA and confirming the involvement of surface glycosylation.
Richter
J
J
Laboratory of Natural Cell Immunity, Section of Immunology and Gnotobiology, Institute of Microbiology, Videnska 1083, 14220 Prague 4, Czech Republic.
Benson
V
V
Grobarova
V
V
Svoboda
J
J
Vencovsky
J
J
Svobodova
R
R
Fiserova
A
A
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology; D002452:Cell Count; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D003882:Dermatomyositis / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids / Q000627:therapeutic use; D006001:Glycoconjugates / Q000494:pharmacology; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000276:immunology; D017285:Polymyositis / Q000276:immunology; D011134:Polysaccharides / Q000494:pharmacology*; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D013582:Synovial Fluid / Q000166:cytology / Q000378:metabolism; D014746:Vimentin / Q000494:pharmacology*
D001323:Autoantibodies; D001324:Autoantigens; D005938:Glucocorticoids; D006001:Glycoconjugates; D007166:Immunosuppressive Agents; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011134:Polysaccharides; D014746:Vimentin; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases