NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.
NCR3/NKp30 contributes to pathogenesis in primary Sjogren's syndrome.
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DOI：
10.1126/scitranslmed.3005727
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发表时间：
2013-07-24
影响因子：
17.1
通讯作者：
Mariette X
中科院分区：
文献类型：
--
作者：
Rusakiewicz S;Nocturne G;Lazure T;Semeraro M;Flament C;Caillat-Zucman S;Sène D;Delahaye N;Vivier E;Chaba K;Poirier-Colame V;Nordmark G;Eloranta ML;Eriksson P;Theander E;Forsblad-d'Elia H;Omdal R;Wahren-Herlenius M;Jonsson R;Rönnblom L;Nititham J;Taylor KE;Lessard CJ;Sivils KL;Gottenberg JE;Criswell LA;Miceli-Richard C;Zitvogel L;Mariette X
原发性干燥综合征（pSS）是一种以淋巴细胞外分泌病为特征的慢性自身免疫性疾病。然而，患者通常有全身性自身免疫的证据，并且他们发生非霍奇金淋巴瘤的风险显著增加。类似于其他自身免疫性疾病，强干扰素（IFN）签名存在于pSS患者的子集中，尽管确切的病因仍不确定。NCR 3/NKp 30是NK特异性活化受体，调节NK和树突状细胞之间的串扰和II型IFN分泌。我们对NCR 3/NKp 30基因的遗传多态性进行了病例对照研究，发现位于启动子的rs 11575837（G>A）与基因转录和功能降低以及对pSS的保护有关。我们还证明，与对照组相比，pSS患者的循环中NCR 3/NKp 30水平显著升高，并且与NK细胞的较高的NCR 3/NKp 30而非CD 16依赖性IFN-γ分泌相关。小唾液腺中NK细胞的过度积累与外分泌病的严重程度相关。NKp 30的配体B7 H6由唾液腺上皮细胞表达。这些发现表明NK细胞可能促进唾液腺中NKp 30依赖性炎症状态，并且B7 H6/NKp 30轴的阻断可能与pSS的临床相关。
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, though the precise etiology remains uncertain. NCR3/NKp30 is a 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 markedly 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.
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影响因子：
12.8
作者：
Chiorini JA;Cihakova D;Ouellette CE;Caturegli P
通讯作者：
Caturegli P
影响因子：
9.1
作者：
Lee, Byung Ha;Gauna, Adrienne E.;Pauley, Kaleb M.;Park, Yun-Jong;Cha, Seunghee
通讯作者：
Cha, Seunghee
影响因子：
2.2
作者：
Al-Hubeshy, Z. B.;Coleman, A.;Goodier, M. R.
通讯作者：
Goodier, M. R.
DOI：
10.1016/0030-4220(74)90417-4
发表时间：
1974-01-01
期刊：
ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY
影响因子：
--
作者：
GREENSPAN, JS;DANIELS, TE;SYLVESTER, RA
通讯作者：
SYLVESTER, RA
影响因子：
20.3
作者：
Bryceson, Yenan T.;Rudd, Eva;Ljunggren, Hans-Gustaf
通讯作者：
Ljunggren, Hans-Gustaf