Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14-tetramethyl-pentadecane (pristane)
Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14-tetramethyl-pentadecane (pristane)
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DOI：
10.2353/ajpath.2006.050125
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发表时间：
2006-04-01
影响因子：
6
通讯作者：
Reeves, WH
中科院分区：
文献类型：
--
作者：
Nacionales, DC;Kelly, KM;Reeves, WH
类风湿新生与抗体介导的自身免疫性疾病如干燥综合征和类风湿性关节炎有关。虽然是系统性狼疮;淋巴结炎是典型的B细胞介导的自身免疫性疾病，淋巴新生在其发病机制中的作用尚不清楚。腹腔注射2，6，10，14-四甲基十五烷（TMPD，降植烷）或矿物油导致小鼠脂肪肉芽肿形成，但只有TMPD治疗的小鼠发展狼疮。我们报告脂肪肉芽肿是淋巴新生的一种形式。脂肪肉芽肿的免疫过氧化物酶染色显示B细胞，CD 4（+）T细胞和树突状细胞，在某些情况下组织成T细胞和B细胞区。脂肉芽肿还表达淋巴样趋化因子CCL 21、CCL 19、CXCL 13、CXCL 12和CCL 22。与矿物油诱导的脂肪肉芽肿相比，TMPD诱导的脂肪肉芽肿中I型干扰素（IFN-I）诱导基因Mx 1、IRF 7、IP-10和ISG-15的表达大大增加。TMPD脂肪肉芽肿的树突状细胞经历活化/成熟，具有高CD 86和白细胞介素-12表达。磁珠耗尽树突状细胞显着减少IFN-诱导基因（Mx 1）的表达。我们的结论是TMPD诱导的狼疮与异位淋巴组织的形成有关，异位淋巴组织中含有活化的树突状细胞，产生IFN-I和白细胞介素-12。鉴于系统性红斑狼疮中IFN-Ⅰ的产生增加，这些研究表明，异位淋巴组织中的IFN-Ⅰ可能在小鼠实验性狼疮的发病机制中发挥作用。
Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus; crythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of lipogranulomas revealed B cells, CD4(+) T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Li-pogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1, IRF7, IP-10, and ISG-15 was greatly increased in TMPD- versus mineral oil-induced lipogranulomas. Dendritic cells from TMPD lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene (Mx1) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.