期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 5, 期 195, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3005727
关键词
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资金
- French Ministry of Health [PHRC 2006-AOM06133, PHRC 2010-AOM10188]
- Direction de la Recherche Clinique, Assistance Publique-Hopitaux de Paris
- French Ministry of Research [ANR- 2010-BLAN-1133 01]
- LIGUE Francaise contre le Cancer (Label) INCA
- Fondation de France
- INFLACARE FP7
- SIRIC Socrates
- LABEX immuno-oncology
- Fondation pour la Recherche Medicale
- Swedish Rheumatism Association
- Swedish Research Council
- Broegelmann Foundation
- Strategic Research Program at Helse Bergen
- NIH [P50 AR0608040, 5R01 DE015223, 5U19 AI082714, 1R01 DE018209-02, 5R01 DE018209, 3P20 RR020143, 5P01 AI083194-03]
- American College of Rheumatology Research and Education Foundation/Abbott Healthy Professional Graduate Student Preceptorship Award
- Oklahoma Medical Research Foundation
- Sjogren's Syndrome Foundation [4434]
- Phileona Foundation
Primary Sjogren'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-gamma 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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