Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjogren's syndrome
Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjogren's syndrome
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DOI：
10.1002/art.23214
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发表时间：
2008-03-01
影响因子：
--
通讯作者：
Peck, Ammon B.
中科院分区：
文献类型：
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作者：
Nguyen, Cuong Q.;Hu, Min H.;Peck, Ammon B.
目标。最近，随着Th17细胞的发现，Th1/Th2模式得到了扩展，Th17细胞是CD4+记忆T细胞的一个亚群，其特征是具有分泌白细胞介素17(IL-17)家族细胞因子的独特能力。重要的是，Th17细胞似乎与自身免疫密切相关。本研究旨在探讨干燥综合征(SS)患者外周血中Th17/IL-23系统是否上调。用免疫组织化学、实时聚合酶链式反应和Luminex系统检测C57BL/6小鼠的血清、唾液和唾液腺组织中IL-17和IL-23的表达。对C57BL16NOD-Aec1Aec2小鼠颌下腺和SS患者唾液腺活检标本的免疫组织化学染色显示，IL-17和IL-23在淋巴灶内呈强阳性染色，在上皮组织中呈弥漫性染色。IL-17和IL-23在C57BL/6小鼠颌下腺中的瞬时表达与Th17细胞主控基因视黄酸相关孤儿受体γt的表达相关。4-20周龄C57BL/6.NOD-Aec1Aec2小鼠唾液中未检测到IL-17，但16周龄小鼠血液中存在IL-17。这与SS患者的血清和唾液不同程度地存在IL-17和IL-6形成对比。这些结果表明，C57BL/6小鼠和SS患者发病时Th17/IL-23系统表达上调。IL-17/IL-23表达上调与SS的特殊临床表现之间的关系尚不明确。
Objective. Recently, the Th1/Th2 paradigm has been expanded by the discovery of Th17 cells, a subset of CD4+ memory T cells characterized by their unique ability to secrete interleukin-17 (IL-17) family cytokines. Importantly, Th17 cells appear to be intimately involved in autoimmunity. We undertook the present study to investigate whether the Th17/IL-23 system is up-regulated in Sjogren's syndrome (SS).Methods. Sera, saliva, and salivary glands from C57BL/6.NOD-Aec1Aec2 mice (a model for primary SS), as well as sera, saliva, and salivary gland biopsy specimens obtained from patients with primary SS, were evaluated for IL-17 and IL-23 expression by immunohistochemistry, real-time polymerase chain reaction, and the Luminex system.Results. Immunohistochemical stainings of submandibular glands from C57BL16.NOD-Aec1Aec2 mice and of salivary gland biopsy specimens from SS patients revealed strong positive staining for both IL-17 and IL-23 within lymphocytic foci and diffuse staining on epithelial tissues. Temporal expression of IL-17 and IL-23 in submandibular glands of C57BL/6.NOD-Aec1Aec2 mice correlated with expression of retinoic acid-related orphan receptor gamma t, the Th17 cell master control gene. While IL-17 could not be detected in saliva from 4-20-week-old C57BL/6.NOD-Aec1Aec2 mice, this cytokine was present in the blood of mice up to age 16 weeks. This contrasted with sera and saliva from SS patients, in which IL-17 and IL-6 were present at varying levels.Conclusion. These results suggest that the Th17/IL-23 system is up-regulated in C57BL/6.NOD-Aec1Aec2 mice and SS patients at the time of disease. A correlation between up-regulated IL-17/IL-23 expression and specific clinical manifestations of SS has yet to be identified.