Interleukin-7 enhances the Th1 response to promote the development of Sjögren's syndrome-like autoimmune exocrinopathy in mice.
Interleukin-7 enhances the Th1 response to promote the development of Sjögren's syndrome-like autoimmune exocrinopathy in mice.
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DOI：
10.1002/art.38007
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发表时间：
2013-08
影响因子：
--
通讯作者：
Yu, Qing
中科院分区：
文献类型：
--
作者：
Jin, Jun-O;Kawai, Toshihisa;Cha, Seunghee;Yu, Qing
尽管在原发性干燥综合征（pSjS）患者中报道了升高的IL-7水平，但IL-7在该疾病中的作用仍不清楚。在此，我们使用重现人pSjS的C57 BL/6. NOD-Aec 1Aec 2（B6.NOD-Aec）小鼠模型表征了IL-7在pSjS的发展和发作中的先前未探索的作用。对于功能获得性研究，将重组IL-7或对照PBS腹膜内（i. p.）NOD-Aec小鼠体内8周。对于功能丧失研究，将中和抗IL-7受体抗体或其同种型对照IgG腹膜内给予16周龄B6.NOD-Aec小鼠。进行唾液流测量、唾液腺组织学和流式细胞术分析以及血清抗核抗体测定以评估各种疾病参数。外源性IL-7的管理加速，而IL-7受体信号传导的阻断几乎完全取消了pSjS的发展，基于唾液腺炎症和细胞凋亡，自身抗体的产生和分泌功能障碍。IL-7正向调节唾液腺中产生IFN-γ的Th 1和CD 8 T细胞，而不影响IL-17。此外，IL-7以T细胞和IFN-γ依赖的方式增强CXCR 3配体的表达。因此，IFN-γ诱导人唾液腺上皮细胞系产生CXCR 3配体。IL-7还增加了TNF-α的水平，TNF-α是另一种Th 1相关的细胞因子，可以促进组织破坏和炎症。IL-7在SjS中起关键的致病作用，其通过增强的Th 1应答和IFN-γ-CXCR 3配体介导的靶器官的淋巴细胞浸润来支持。这些结果表明，靶向IL-7通路可能是未来预防和治疗SjS的潜在策略。
Although elevated IL-7 levels were reported in patients with primary Sjӧgren’s syndrome (pSjS), the role of IL-7 in this disease remains unclear. Here we characterized the previously unexplored role of IL-7 in the development and onset of pSjS using C57BL/6.NOD-Aec1Aec2 (B6.NOD-Aec) mouse model that recapitulates human pSjS. For gain-of-function studies, recombinant IL-7 or control PBS was injected intraperitoneally (i.p.) into 12-week old B6.NOD-Aec mice for 8 weeks. For loss-of-function studies, neutralizing anti-IL-7 receptor antibody or its isotype control IgG was administered i.p. into 16-week old B6.NOD-Aec mice. Salivary flow measurement, histological and flow cytometric analysis of salivary glands, and serum antinuclear antibody assay were performed to assess various disease parameters. Administration of exogenous IL-7 accelerated, whereas blockade of IL-7 receptor signaling almost completely abolished the development of pSjS, based on salivary gland inflammation and apoptosis, autoantibody production and secretory dysfunction. IL-7 positively regulated IFN-γ-producing Th1 and CD8 T cells in the salivary glands without affecting IL-17. Moreover, IL-7 enhanced the expression of CXCR3 ligands in a T cell- and IFN-γ-dependent fashion. Accordingly, IFN-γ induced a human salivary gland epithelial cell line to produce CXCR3 ligands. IL-7 also increased the level of TNF-α, another Th1-associated cytokine that can facilitate tissue destruction and inflammation. IL-7 plays a pivotal pathogenic role in SjS, which is underpinned by an enhanced Th1 response and IFN-γ-CXCR3 ligand-mediated lymphocyte infiltration of target organs. These results suggest that targeting IL-7 pathway may be a potential future strategy to prevent and treat SjS.
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DOI：
10.1111/j.1600-0714.2008.00700.x
发表时间：
2009-01
期刊：
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
影响因子：
--
作者：
Deshmukh US;Nandula SR;Thimmalapura PR;Scindia YM;Bagavant H
通讯作者：
Bagavant H
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
5.5
作者：
Bikker, Angela;Moret, Frederique M.;van Roon, Joel A. G.
通讯作者：
van Roon, Joel A. G.
影响因子：
3.7
作者：
Groom JR;Luster AD
通讯作者：
Luster AD
DOI：
10.1111/j.1749-6632.2009.04813.x
发表时间：
2009-01-01
期刊：
CONTEMPORARY CHALLENGES IN AUTOIMMUNITY
影响因子：
--
作者：
Lacotte, Stephanie;Brun, Susana;Dumortier, Helene
通讯作者：
Dumortier, Helene