Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages.
Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages.
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DOI：
10.1038/ncomms4039
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发表时间：
2014
影响因子：
16.6
通讯作者：
Botto M
中科院分区：
文献类型：
--
作者：
Ling GS;Bennett J;Woollard KJ;Szajna M;Fossati-Jimack L;Taylor PR;Scott D;Franzoso G;Cook HT;Botto M
巨噬细胞和树突状细胞对脂多糖（LPS）诱导的Toll样受体4（TLR4）活化的调谐和不同的反应支持先天性免疫和适应性免疫之间的平衡。然而，赋予这些细胞类型特异性LPS诱导作用的分子仍然知之甚少。在这里，我们报告，整合素αM（CD11b）积极调节LPS诱导的信号转导通路选择性髓样树突状细胞，而不是在巨噬细胞。在树突状细胞中，其表达的CD14和TLR4水平低于巨噬细胞，CD11b促进MyD88依赖性和MyD88非依赖性信号通路。特别是，在树突状细胞中，CD11b促进LPS诱导的TLR4内吞作用，并且是内体中后续信号传导所需的。与此相一致，CD11b缺乏抑制树突状细胞介导的TLR4触发的体内反应，导致受损的T细胞活化。因此，通过以细胞类型特异性方式调节TLR4的运输和信号传导功能，CD11b微调LPS引发的适应性和先天性免疫应答之间的平衡。 赋予树突状细胞和巨噬细胞对LPS的反应差异的信号通路仍然知之甚少。在此，Ling等人报道了整合素C11b是LPS诱导的树突细胞中的TLR4运输和信号传导所必需的，但在巨噬细胞中不是。
Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin αM (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS. The signalling pathways that confer differences in the responses of dendritic cells and macrophages to LPS remain poorly understood. Here, Ling et al. report that the integrin C11b is required for LPS-induced TLR4 trafficking and signalling in dendritic cells but not in macrophages.
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DOI：
10.4049/jimmunol.0901296
发表时间：
2010-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jones SC;Brahmakshatriya V;Huston G;Dibble J;Swain SL
通讯作者：
Swain SL
影响因子：
30.5
作者：
Lantz, O;Grandjean, I;Di Santo, JP
通讯作者：
Di Santo, JP
影响因子：
4.4
作者：
Perera, PY;Mayadas, TN;Vogel, SN
通讯作者：
Vogel, SN
影响因子：
5.5
作者：
Lapilla, Marilena;Gallo, Barbara;Pedotti, Rosetta
通讯作者：
Pedotti, Rosetta
DOI：
10.1084/jem.20031076
发表时间：
2003-10-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Akashi S;Saitoh S;Wakabayashi Y;Kikuchi T;Takamura N;Nagai Y;Kusumoto Y;Fukase K;Kusumoto S;Adachi Y;Kosugi A;Miyake K
通讯作者：
Miyake K