title: NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.
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.
authors.affiliation: INSERM U1015, Institut Gustave Roussy (IGR), 94805 Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.forename: Gaetane
authors.initials: G
authors.lastname: Nocturne
authors.forename: Thierry
authors.initials: T
authors.lastname: Lazure
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.forename: Caroline
authors.initials: C
authors.lastname: Flament
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillat-Zucman
authors.forename: Damien
authors.initials: D
authors.lastname: Sène
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delahaye
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Kariman
authors.initials: K
authors.lastname: Chaba
authors.forename: Vichnou
authors.initials: V
authors.lastname: Poirier-Colame
authors.forename: Gunnel
authors.initials: G
authors.lastname: Nordmark
authors.forename: Maija-Leena
authors.initials: ML
authors.lastname: Eloranta
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Elke
authors.initials: E
authors.lastname: Theander
authors.forename: Helena
authors.initials: H
authors.lastname: Forsblad-d'Elia
authors.forename: Roald
authors.initials: R
authors.lastname: Omdal
authors.forename: Marie
authors.initials: M
authors.lastname: Wahren-Herlenius
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
authors.forename: Lars
authors.initials: L
authors.lastname: Rönnblom
authors.forename: Joanne
authors.initials: J
authors.lastname: Nititham
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Taylor
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lessard
authors.forename: Kathy L Moser
authors.initials: KL
authors.lastname: Sivils
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Corinne
authors.initials: C
authors.lastname: Miceli-Richard
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D000328:Adult; D000368:Aged; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000097:blood* / Q000235:genetics*
chemical_list: C573415:IFNG protein, human; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D007371:Interferon-gamma