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NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.

Sylvie Rusakiewicz 1, 2 Gaetane Nocturne 3 Thierry Lazure 4 Michaela Semeraro 1, 2 Caroline Flament 1, 2, 5 Sophie Caillat-Zucman 6 D. Sene Nicolas Delahaye 2 Eric Vivier 7 Kariman Chaba 8 Vichnou Poirier-Colame 2 Gunnel Nordmark 9 L. Eloranta Per Eriksson Elke Theander 10 Helena Forsblad-d'Elia Roald Omdal Marie Wahren-Herlenius Roland Jonsson 11 L. Ronnblom 9 Joanne Nititham 12 Kimberly E Taylor 12 Christopher J Lessard 13 L. Sivils Jacques-Eric Gottenberg 14 Lindsey A Criswell 12 Corinne Miceli-Richard 3, 15 Laurence Zitvogel 2, 1 Xavier Mariette 15, 3 Damien Sène Maija-Leena Eloranta 9 Lars Rönnblom 9 Kathy L Moser Sivils 13 Alain Saraux 16, 17, 18
1 CIC 1428 , CBT 507 - Centre d'Investigation Clinique en Biotherapie des cancers
2 UMR 1015 - Immunologie des tumeurs et immunothérapie
3 Régulation de la réponse immune, infection VIH-1 et autoimmunité
4 AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
5 CEA-DES (ex-DEN) - CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire)
6 Inserm U986
7 CIML - Centre d'Immunologie de Marseille - Luminy
8 CRC - Inserm U1138 - Immunologie et Cancérologie Intégratives
CRC - Centre de Recherche des Cordeliers
9 Department of Medical Sciences
10 Dep Rheumato - Malmo - SUEDE - Department of Rheumatology
11 FOI - Swedish Defence Research Agency [Stockholm]
12 Rosalind Russell Medical Research Center for Arthritis
13 OUHSC - University of Oklahoma Health Sciences Center
14 Immuno-Rhumatologie Moléculaire
15 Service de rhumatologie
16 CIC 1412 - BREST - Centre d'Investigation Clinique INSERM 1412
17 LBAI - Lymphocyte B et Auto-immunité
18 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
Abstract : Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non- Hodgkin's lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (G>A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-γ secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.
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Journal articles
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https://hal.univ-brest.fr/hal-01558189
Contributor : Ghislaine Calvez <>
Submitted on : Friday, July 7, 2017 - 11:50:02 AM
Last modification on : Friday, September 18, 2020 - 2:34:58 PM

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  • HAL Id : hal-01558189, version 1
  • PUBMED : 23884468

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Citation

Sylvie Rusakiewicz, Gaetane Nocturne, Thierry Lazure, Michaela Semeraro, Caroline Flament, et al.. NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.. Science Translational Medicine, American Association for the Advancement of Science, 2013, 5 (195), pp.195ra96. ⟨hal-01558189⟩

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