Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts

Natasja Nielsen; Veronique Pascal; Andreas E R Fasth; Yvonne Sundström; Elisabeth D Galsgaard; David Ahern; Martin Andersen; Bo Baslund; Else M Bartels; Henning Bliddal; Marc Feldmann; Vivianne Malmström; Louise Berg; Pieter Spee; Kalle Söderström

doi:10.1111/imm.12271

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts

Natasja Nielsen, Veronique Pascal, Andreas E R Fasth, Yvonne Sundström, Elisabeth D Galsgaard, David Ahern, Martin Andersen, Bo Baslund, Else M Bartels, Henning Bliddal, Marc Feldmann, Vivianne Malmström, Louise Berg, Pieter Spee, Kalle Söderström

Department of Clinical Medicine

20 Citations (Scopus)

Abstract

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 CD94/NKG2A 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 NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A 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.

Original language	English
Journal	Immunology
Volume	142
Issue number	4
Pages (from-to)	581-593
Number of pages	13
ISSN	0019-2805
DOIs	https://doi.org/10.1111/imm.12271
Publication status	Published - Aug 2014

Keywords

Antigens, Differentiation, T-Lymphocyte
Arthritis, Rheumatoid
Cell Degranulation
Cell Line
Female
Fibroblasts
Histocompatibility Antigens Class I
Humans
Killer Cells, Natural
Male
NK Cell Lectin-Like Receptor Subfamily C
NK Cell Lectin-Like Receptor Subfamily D
NK Cell Lectin-Like Receptor Subfamily K
Natural Cytotoxicity Triggering Receptor 1
Natural Cytotoxicity Triggering Receptor 2
Synovial Membrane
Up-Regulation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/imm.12271

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Nielsen, N., Pascal, V., Fasth, A. E. R., Sundström, Y., Galsgaard, E. D., Ahern, D., Andersen, M., Baslund, B., Bartels, E. M., Bliddal, H., Feldmann, M., Malmström, V., Berg, L., Spee, P., & Söderström, K. (2014). Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts. Immunology, 142(4), 581-593. https://doi.org/10.1111/imm.12271

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts. / Nielsen, Natasja; Pascal, Veronique; Fasth, Andreas E R et al.

In: Immunology, Vol. 142, No. 4, 08.2014, p. 581-593.

Research output: Contribution to journal › Journal article › Research › peer-review

Nielsen, N, Pascal, V, Fasth, AER, Sundström, Y, Galsgaard, ED, Ahern, D, Andersen, M, Baslund, B, Bartels, EM, Bliddal, H, Feldmann, M, Malmström, V, Berg, L, Spee, P & Söderström, K 2014, 'Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts', Immunology, vol. 142, no. 4, pp. 581-593. https://doi.org/10.1111/imm.12271

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title = "Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts",

abstract = "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 CD94/NKG2A 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 NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A 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.",

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author = "Natasja Nielsen and Veronique Pascal and Fasth, {Andreas E R} and Yvonne Sundstr{\"o}m and Galsgaard, {Elisabeth D} and David Ahern and Martin Andersen and Bo Baslund and Bartels, {Else M} and Henning Bliddal and Marc Feldmann and Vivianne Malmstr{\"o}m and Louise Berg and Pieter Spee and Kalle S{\"o}derstr{\"o}m",

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volume = "142",

pages = "581--593",

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T1 - Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts

AU - Nielsen, Natasja

AU - Pascal, Veronique

AU - Fasth, Andreas E R

AU - Sundström, Yvonne

AU - Galsgaard, Elisabeth D

AU - Ahern, David

AU - Andersen, Martin

AU - Baslund, Bo

AU - Bartels, Else M

AU - Bliddal, Henning

AU - Feldmann, Marc

AU - Malmström, Vivianne

AU - Berg, Louise

AU - Spee, Pieter

AU - Söderström, Kalle

PY - 2014/8

Y1 - 2014/8

N2 - 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 CD94/NKG2A 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 NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A 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.

AB - 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 CD94/NKG2A 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 NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A 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.

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KW - Arthritis, Rheumatoid

KW - Cell Degranulation

KW - Cell Line

KW - Female

KW - Fibroblasts

KW - Histocompatibility Antigens Class I

KW - Humans

KW - Killer Cells, Natural

KW - Male

KW - NK Cell Lectin-Like Receptor Subfamily C

KW - NK Cell Lectin-Like Receptor Subfamily D

KW - NK Cell Lectin-Like Receptor Subfamily K

KW - Natural Cytotoxicity Triggering Receptor 1

KW - Natural Cytotoxicity Triggering Receptor 2

KW - Synovial Membrane

KW - Up-Regulation

U2 - 10.1111/imm.12271

DO - 10.1111/imm.12271

M3 - Journal article

C2 - 24673109

SN - 0953-4954

VL - 142

SP - 581

EP - 593

JO - Immunology. Supplement

JF - Immunology. Supplement

IS - 4

ER -

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts

Abstract

Keywords

UN SDGs

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