Body-barrier surveillance by epidermal γδ TCRs.

Body-barrier surveillance by epidermal γδ TCRs.
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DOI:
10.1038/ni.2240
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发表时间:
2012-02-12
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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对身体屏障的监测依赖于常驻T细胞,其谱系根据位置偏向于特定的γδT细胞受体谱系。这些γδTCR被证明能够识别应激反应配体。利用活体动态免疫信号相关显微镜,我们报道了表皮T细胞表达的V-γ-5 TCR在体内稳定状态下结构性聚集和功能激活,形成真正的免疫突触,极化并锚定T细胞在鳞状角质形成细胞紧密连接处的投射。这种突触发生依赖于TcR可变区、LCK和αE(CD103)β7-整合素,而不依赖于γδ谱系或NKG2D。在对组织应力的响应中,TCR近端信号没有显著增加,但经历了应力模式依赖的重新定位。因此,γδTCR可能通过识别稳定表达的组织配体来主动协调屏障监测。
The surveillance of body barriers relies on resident T cells whose repertoires are biased toward particular γδ T cell receptor lineages according to location. These γδ TCRs were shown to recognize stress-emergent ligands. Using intravital dynamics-immunosignal correlative microscopy, we report that epidermal T cell-expressed Vγ5 TCRs were constitutively clustered and functionally activated in vivo at steady-state, forming bona-fide immunological synapses that polarized and anchored T cell projections at squamous keratinocyte tight junctions. This synaptogenesis depended on TCR variable domains, Lck and αE(CD103)β7-integrin, but not the γδ lineage or NKG2D. In response to tissue stress, TCR-proximal signals did not increase significantly but underwent stress mode-dependent re-localization. Thus, the γδ TCR orchestrates barrier surveillance pro-actively, presumably by recognizing steady-state-expressed tissue ligands.
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