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 Hôpital Bicêtre [AP-HP, 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
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 IRM - Immuno-Rhumatologie Moléculaire
15 Service de rhumatologie
16 CIC - Brest - Centre d'Investigation Clinique
17 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
18 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
2 UMR 1015 - Immunologie des tumeurs et immunothérapie
3 Régulation de la réponse immune, infection VIH-1 et autoimmunité
4 Hôpital Bicêtre [AP-HP, 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
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 IRM - Immuno-Rhumatologie Moléculaire
15 Service de rhumatologie
16 CIC - Brest - Centre d'Investigation Clinique
17 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
18 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
Gaetane Nocturne
- Fonction : Auteur
- PersonId : 775605
- ORCID : 0000-0001-6809-0733
Sophie Caillat-Zucman
- Fonction : Auteur
- PersonId : 756202
- ORCID : 0000-0002-4535-3550
- IdRef : 06997229X
D. Sene
- Fonction : Auteur
Eric Vivier
- Fonction : Auteur
- PersonId : 17342
- IdHAL : eric-vivier
- ORCID : 0000-0001-7022-8287
- IdRef : 076121712
L. Eloranta
- Fonction : Auteur
Per Eriksson
- Fonction : Auteur
Elke Theander
- Fonction : Auteur
- PersonId : 761899
- ORCID : 0000-0002-6533-2263
Helena Forsblad-d'Elia
- Fonction : Auteur
Roald Omdal
- Fonction : Auteur
Marie Wahren-Herlenius
- Fonction : Auteur
L. Sivils
- Fonction : Auteur
Jacques-Eric Gottenberg
- Fonction : Auteur
- PersonId : 756827
- ORCID : 0000-0002-9469-946X
Corinne Miceli-Richard
- Fonction : Auteur
- PersonId : 1134718
- ORCID : 0000-0002-3009-3637
- IdRef : 089428854
Laurence Zitvogel
- Fonction : Auteur
- PersonId : 756204
- IdHAL : laurence-zitvogel
- ORCID : 0000-0003-1596-0998
- IdRef : 083439587
Xavier Mariette
- Fonction : Auteur
- PersonId : 756829
- ORCID : 0000-0002-4244-5417
- IdRef : 113094116
Damien Sène
- Fonction : Auteur
Alain Saraux
- Fonction : Autre
- PersonId : 762362
- ORCID : 0000-0002-8454-7067
Résumé
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.