CD161 receptor participates in both impairing NK cell cytotoxicity and the response to glycans and vimentin in patients with rheumatoid arthritis J. Richter a , V. Benson a , V. Grobarova a , J. Svoboda a , J. Vencovsky b , R. Svobodova b , A. Fiserova a, ⁎ a Laboratory of Natural Cell Immunity, Section of Immunology and Gnotobiology, Institute of Microbiology, Videnska 1083, 14220 Prague 4, Czech Republic b Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic Received 16 December 2009; accepted with revision 10 March 2010 Available online 31 March 2010 KEYWORDS CD161; Rheumatoid arthritis; NK cells; MCV; PAD4; Glycosylation; MGAT5 Abstract 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 b 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. © 2010 Elsevier Inc. All rights reserved. Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the synovial tissue in multiple joints. Inflamma- tion in RA and other rheumatoid diseases is mediated by activation of T cells, leading to activation of macrophages and fibroblast-like synoviocytes that subsequently produce proinflammatory cytokines. Synovial tissue proliferation is associated with destruction of cartilage and bone; the closely related production of proteinases (MMPs), which degrade collagen and proteoglycans, serves to further antigenically challenge the immune system [1]. Innate immunity is likely to be of critical importance in the development and regulation of autoimmunity. However, the cells, receptors, and mediators involved in various autoimmune conditions are mostly unknown. Natural killer ⁎ Corresponding author. Laboratory of Natural Cell Immunity, Department of Immunology and Gnotobiology, Institute of Microbi- ology AS CR v. v. i., Videnska 1083, 14220, Prague 4, Czech Republic. Fax: +420 296 442 106. E-mail address: fiserova@biomed.cas.cz (A. Fiserova). 1521-6616/$ - see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2010.03.005 available at www.sciencedirect.com Clinical Immunology www.elsevier.com/locate/yclim Clinical Immunology (2010) 136, 139–147