NCR3/NKp30 Contributes to Pathogenesis in Primary Sjogren's Syndrome

被引：103

作者：

Rusakiewicz, Sylvie ^{[1
,2
,3
]}

Nocturne, Gaetane ^{[3
,4
]}

Lazure, Thierry ^{[5
]}

Semeraro, Michaela ^{[2
,6
]}

Flament, Caroline ^{[1
,2
]}

Caillat-Zucman, Sophie ^{[7
,9
]}

Sene, Damien ^{[7
,8
,9
]}

Delahaye, Nicolas ^{[1
]}

Vivier, Eric ^{[10
,11
]}

Chaba, Kariman ^{[1
,12
]}

Poirier-Colame, Vichnou ^{[1
,2
]}

Nordmark, Gunnel ^{[13
]}

Eloranta, Maija-Leena ^{[13
]}

Eriksson, Per ^{[14
]}

Theander, Elke ^{[15
]}

Forsblad-d'Elia, Helena ^{[16
]}

Omdal, Roald ^{[17
]}

Wahren-Herlenius, Marie ^{[18
]}

Jonsson, Roland ^{[19
]}

Ronnblom, Lars ^{[13
]}

Nititham, Joanne ^{[20
]}

Taylor, Kimberly E. ^{[20
]}

Lessard, Christopher J. ^{[21
,22
]}

Sivils, Kathy L. Moser ^{[21
,22
]}

Gottenberg, Jacques-Eric ^{[23
]}

Criswell, Lindsey A. ^{[20
]}

Miceli-Richard, Corinne ^{[1
,24
]}

Zitvogel, Laurence ^{[1
,2
,3
,4
]}

Mariette, Xavier ^{[3
,4
,24
]}

机构：

[1] IGR, INSERM, U1015, F-94805 Villejuif, France

[2] IGR, CICBT507, Ctr Clin Invest, F-94805 Villejuif, France

[3] Univ Paris Sud, Fac Med, F-92476 Le Kremlin Bicetre, France

[4] Univ Paris Sud, INSERM, U1012, F-92476 Le Kremlin Bicetre, France

[5] Hop Univ Paris Sud, AP HP, Dept Pathol, F-94275 Le Kremlin Bicetre, France

[6] IGR, Dep Oncol Pediat, F-94805 Villejuif, France

[7] Hop St Vincent De Paul, INSERM, U986, F-75014 Paris, France

[8] Gru Hosp Lariboisisere, AP HP, Dept Internal Med, F-75010 Paris, France

[9] Univ Paris Diderot, Paris, France

[10] INSERM, Ctr Immunol Marseille Luminy, INSERM, U1104, F-13009 Marseille, France

[11] CNRS, UMR7280, F-13288 Marseille, France

[12] Univ Paris 05, F-75006 Paris, France

[13] Uppsala Univ, Dept Med Sci, Rheumatol, SE-75185 Uppsala, Sweden

[14] Linkoping Univ, Dept Clin & Expt Med, Rheumatol AIR, SE-58183 Linkoping, Sweden

[15] Lund Univ, Skane Univ Hosp, SE-20502 Malmo, Sweden

[16] Univ Gothenburg, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, S-40530 Gothenburg, Sweden

[17] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, N-4068 Stavanger, Norway

[18] Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden

[19] Univ Bergen, Gade Inst, Broegelmann Res Lab, NO-5020 Bergen, Norway

[20] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA 94117 USA

[21] Oklahoma Med Res Fdn, Arthritis & Clin Immunol Res Program, Oklahoma City, OK 73104 USA

[22] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA

[23] Strasbourg Univ Hosp, Hop Hautepierre, EA 4438, Dept Rheumatol, F-67000 Strasbourg, France

[24] Hop Univ Paris Sud, AP HP, Dept Rheumatol, F-94275 Le Kremlin Bicetre, France

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2013年 / 5卷 / 195期

基金：

瑞典研究理事会;

关键词：

SALIVARY-GLANDS; PERIPHERAL-BLOOD; DENDRITIC CELLS; NK CELLS; EXPRESSION; ASSOCIATION; RECEPTOR; ACTIVATION; SECRETION; DISEASE;

D O I：

10.1126/scitranslmed.3005727

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：10

共 55 条

[1] Lack of Il12rb2 signaling predisposes to,spontaneous autoimmunity and malignancy [J].