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

Rusakiewicz, Sylvie ; Nocturne, Gaetane ; Lazure, Thierry ; Semeraro, Michaela ; Flament, Caroline ; Caillat-Zucman, Sophie ; Sene, Damien ; Delahaye, Nicolas ; Vivier, Eric and Chaba, Kariman , et al. (2013) In Science Translational Medicine 5(195). p.96-195
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Translational Medicine
volume
5
issue
195
pages
96 - 195
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • wos:000322233400008
  • scopus:84882999456
ISSN
1946-6242
DOI
10.1126/scitranslmed.3005727
language
English
LU publication?
yes
id
e94c095e-5dfc-4544-a8c4-c56825b48c9e (old id 4042949)
date added to LUP
2016-04-01 10:45:03
date last changed
2020-10-07 01:53:27
@article{e94c095e-5dfc-4544-a8c4-c56825b48c9e,
  abstract     = {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.},
  author       = {Rusakiewicz, Sylvie and Nocturne, Gaetane and Lazure, Thierry and Semeraro, Michaela and Flament, Caroline and Caillat-Zucman, Sophie and Sene, Damien and Delahaye, Nicolas and Vivier, Eric and Chaba, Kariman and Poirier-Colame, Vichnou and Nordmark, Gunnel and Eloranta, Maija-Leena and Eriksson, Per and Theander, Elke and Forsblad-d'Elia, Helena and Omdal, Roald and Wahren-Herlenius, Marie and Jonsson, Roland and Ronnblom, Lars and Nititham, Joanne and Taylor, Kimberly E. and Lessard, Christopher J. and Sivils, Kathy L. Moser and Gottenberg, Jacques-Eric and Criswell, Lindsey A. and Miceli-Richard, Corinne and Zitvogel, Laurence and Mariette, Xavier},
  issn         = {1946-6242},
  language     = {eng},
  number       = {195},
  pages        = {96--195},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Translational Medicine},
  title        = {NCR3/NKp30 Contributes to Pathogenesis in Primary Sjogren's Syndrome},
  url          = {http://dx.doi.org/10.1126/scitranslmed.3005727},
  doi          = {10.1126/scitranslmed.3005727},
  volume       = {5},
  year         = {2013},
}