TY - JOUR
T1 - NCR3/NKp30 Contributes to Pathogenesis in Primary Sjogren's Syndrome
AU - Rusakiewicz, Sylvie
AU - Nocturne, Gaetane
AU - Lazure, Thierry
AU - Semeraro, Michaela
AU - Flament, Caroline
AU - Caillat-Zucman, Sophie
AU - Sene, Damien
AU - Delahaye, Nicolas
AU - Vivier, Eric
AU - Chaba, Kariman
AU - Poirier-Colame, Vichnou
AU - Nordmark, Gunnel
AU - Eloranta, Maija-Leena
AU - Eriksson, Per
AU - Theander, Elke
AU - Forsblad-d'Elia, Helena
AU - Omdal, Roald
AU - Wahren-Herlenius, Marie
AU - Jonsson, Roland
AU - Ronnblom, Lars
AU - Nititham, Joanne
AU - Taylor, Kimberly E.
AU - Lessard, Christopher J.
AU - Sivils, Kathy L. Moser
AU - Gottenberg, Jacques-Eric
AU - Criswell, Lindsey A.
AU - Miceli-Richard, Corinne
AU - Zitvogel, Laurence
AU - Mariette, Xavier
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
U2 - 10.1126/scitranslmed.3005727
DO - 10.1126/scitranslmed.3005727
M3 - Article
SN - 1946-6242
VL - 5
SP - 195ra96
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 195
ER -