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Balance between activating NKG 2D, DNAM ‐1, NK p44 and NK p46 and inhibitory CD 94/ NKG 2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts
Author(s) -
Nielsen Natasja,
Pascal Veronique,
Fasth Andreas E. R.,
Sundström Yvonne,
Galsgaard Elisabeth D.,
Ahern David,
Andersen Martin,
Baslund Bo,
Bartels Else M.,
Bliddal Henning,
Feldmann Marc,
Malmström Vivianne,
Berg Louise,
Spee Pieter,
Söderström Kalle
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12271
Subject(s) - degranulation , receptor , microbiology and biotechnology , cell , immunology , biology , cancer research , chemistry , biochemistry , genetics
Summary Rheumatoid arthritis ( RA ) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast‐like synoviocytes ( FLS ) are central components of the aggressive, tumour‐like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer ( NK ) cell subset expressing the inhibitory CD 94/ NKG 2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA ‐ FLS and NK cells. We used cultured RA ‐ FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA ‐ FLS / NK cell cross‐talk. We show that RA ‐ FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG 2D, DNAM ‐1, NK p46 and NK p44 are the key activating receptors involved in Nishi cell degranulation towards RA ‐ FLS . Moreover, blockade of the interaction between CD 94/ NKG 2A and its ligand HLA ‐E expressed on RA ‐ FLS further enhanced Nishi cell degranulation in co‐culture with RA ‐ FLS . Using cultured RA ‐ FLS and the human NK cell line Nishi as an in vitro model system of RA ‐ FLS / NK cell cross‐talk, our results suggest that cell‐mediated cytotoxicity of RA ‐ FLS may be one mechanism by which NK cells influence local joint inflammation in RA .