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

Sylvie Rusakiewicz; Gaetane Nocturne; Thierry Lazure; Michaela Semeraro; Caroline Flament; Sophie Caillat-Zucman; D. Sene; Nicolas Delahaye; Eric Vivier; Kariman Chaba; Vichnou Poirier-Colame; Gunnel Nordmark; L. Eloranta; Per Eriksson; Elke Theander; Helena Forsblad-D'Elia; Roald Omdal; Marie Wahren-Herlenius; Roland Jonsson; L. Ronnblom; Joanne Nititham; Kimberly E Taylor; Christopher J Lessard; L. Sivils; Jacques-Eric Gottenberg; Lindsey A Criswell; Corinne Miceli-Richard; Laurence Zitvogel; Xavier Mariette; Damien Sène; Maija-Leena Eloranta; Lars Rönnblom; Kathy L Moser Sivils; Alain Saraux

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-DEN - CEA-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.

Type de document :

Article dans une revue

Science Translational Medicine, American Association for the Advancement of Science, 2013, 5 (195), pp.195ra96

Domaine :

Sciences du Vivant [q-bio]

Sciences du Vivant [q-bio] / Médecine humaine et pathologie

Sciences du Vivant [q-bio] / Médecine humaine et pathologie / Rhumatologie et système ostéo-articulaire

Liste complète des métadonnées

http://hal.univ-brest.fr/hal-01558189
Contributeur : Ghislaine Calvez <>
Soumis le : vendredi 7 juillet 2017 - 11:50:02
Dernière modification le : mercredi 2 mai 2018 - 10:56:02

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

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