Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: Selective expression of TLR3 in dendritic cells

Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: Selective expression of TLR3 in dendritic cells
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DOI:
10.4049/jimmunol.164.11.5998
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发表时间:
2000-06-01
影响因子:
4.4
通讯作者:
Mantovani, A
Mantovani, A
中科院分区:
医学2区
文献类型:
--
作者:
Muzio, M;Bosisio, D;Mantovani, A

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Toll样受体(TLR)家族成员可能在病原体识别和先天免疫激活中发挥重要作用。本研究采用系统的方法分析了不同人类白细胞群体如何表达TLR家族前五个成员的特异性转录本。TLR 1在所有检查的白细胞中表达,包括单核细胞、多形核白细胞、T和B细胞以及NK细胞。相反,TLR 2、TLR 4和TLR 5在骨髓单核细胞成分中表达。暴露于细菌产物如LPS或脂阿拉伯甘露聚糖或促炎细胞因子增加了单核细胞和多形核白细胞中的TLR 4表达,而IL-10阻断了这种作用,TLR 3仅在人树突状细胞(DC)中表达,其中细菌产物或细胞因子诱导的成熟与表达减少相关。原位杂交检测DC和淋巴结中TLR 3 mRNA的表达。这些结果表明,TLR 1至TLR 5 mRNA在人白细胞中差异表达和调节。特别地,TLR 3转录物的表达仅限于DC,DC是表达完整TLR库的唯一元件。这些数据表明TLR可以基于表达模式分类为普遍存在的(TLR 1)、限制性的(骨髓单核细胞中的TLR 2、TLR 4和TLR 5)和特异性的(DC中的TLR 3)分子。
Members of the Toll-like receptor (TLR) family probably play a fundamental role in pathogen recognition and activation of innate immunity, The present study used a systematic approach to analyze how different human leukocyte populations express specific transcripts for the first five characterized TLR family members. TLR1 was expressed in all leukocytes examined, including monocytes, polymorphonuclear leukocytes, T and B cells, and NK cells. In contrast TLR2, TLR4, and TLR5 were expressed in myelomonocytic elements, Exposure to bacterial products, such as LPS or lipoarabinomannan, or to proinflammatory cytokines increased TLR4 expression in monocytes and polymorphonuclear leukocytes, whereas IL-IO blocked this effect, TLR3 was only expressed in human dendritic cells (DC) wherein maturation induced by bacterial products or cytokines was associated with reduced expression. TLR3 mRNA expression was detected by in situ hybridization in DC and lymph nodes. These results demonstrate that TLR1 through TLR5 mRNAs are differentially expressed and regulated in human leukocytes. In particular, expression of TLR3 transcripts is restricted to DC that are the only elements which express the full TLR repertoire. These data suggest that TLR can be classified based on expression pattern as ubiquitous (TLR1), restricted (TLK2, TLR4, and TLR5 in myelomonocytic cells), and specific (TLR3 in DC) molecules.