Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways
Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways
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DOI：
10.1002/eji.200738013
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发表时间：
2008-04-01
影响因子：
5.4
通讯作者：
Mariette, Xavier
中科院分区：
文献类型：
--
作者：
Ittah, Marc;Miceli-Richard, Corinne;Mariette, Xavier
B细胞激活因子(BAFF)在促进B淋巴细胞活化中起关键作用。我们研究了危险信号是否诱导唾液腺上皮细胞(SGEC)分泌BAFF，SGEC是原发干燥综合征(一种典型的系统性自身免疫性疾病)的靶标。SGEC培养取自10例有PSS或Sicca症状的患者的小涎腺。用激动剂或病毒刺激不同的Toll样受体(TLR)，检测Baff基因和蛋白的表达。在SGEC中检测到TLR2、-3和-7的表达。Poly(I：C)(合成的TLR3激动剂)和呼肠孤病毒(dsRNA病毒)诱导BAFF基因的高表达(扫描电子显微镜的倍数分别为246+/-39和347+/-66)和BAFF蛋白的高分泌(58.49+/-4.34pg/mL和69.73+/-5.67)。抑制内体途径(用氯喹)和干扰素(用抗IFNAR抗体)部分抑制BAFF的表达。双链RNA病毒和Poly(I：C)均可通过依赖和不依赖TLR、依赖和非依赖干扰素的途径诱导SGEC高水平表达BAFF mRNA和蛋白。病毒感染后自身免疫性疾病靶器官诱导的BAFF可能是先天免疫和自身免疫之间的联系。
B cell activating factor (BAFF) plays a key role in promoting B lymphocyte activation. We investigated whether danger signals induce BAFF secretion by cultured salivary gland epithelial cells (SGEC), which are the target of primary Sjogren's syndrome, a prototypic systemic autoimmune disease. SGEC cultures were established from minor salivary glands obtained from ten patients with pSS or sicca symptoms. BAFF mRNA and protein were measured after stimulation of the different Toll-like receptors (TLR) by agonists or viruses. The expression of TLR2, -3, and -7 was detected in SGEC. Poly (I:C) (a synthetic TLR3 agonist) and reovirus-1 (a dsRNA virus) induced high expression of BAFF mRNA (multiplied by a factor of 246 +/- 39 (SEM) and 347 +/- 66, respectively) and of BAFF protein secretion (58.49 +/- 4.34 pg/mL and 69.73 +/- 5.67). Inhibition of both the endosomal (by chloroquine) and IFN (by anti-IFNAR antibody) pathways partly inhibited BAFF expression. Treatment with both dsRNA virus and poly (I:C) induced high levels of BAFF mRNA and protein expression by SGEC, through pathways dependent on and independent of TLR and dependent on and independent of IFN. BAFF induction by target organs of autoimmune diseases after viral infection may be a link between innate immunity and autoimmunity.