Involvement of an NKG2D Ligand H60c in Epidermal Dendritic T Cell-Mediated Wound Repair
Involvement of an NKG2D Ligand H60c in Epidermal Dendritic T Cell-Mediated Wound Repair
复制标题
DOI：
10.4049/jimmunol.1102886
复制
发表时间：
2012-04-15
影响因子：
4.4
通讯作者：
Kasahara, Masanori
中科院分区：
文献类型：
--
作者：
Yoshida, Shigeru;Mohamed, Rania Hassan;Kasahara, Masanori
在小鼠皮肤中发现的树突状表皮T细胞（DETC）是参与免疫监视和伤口修复的NKG 2D阳性γ δ T细胞。假设DETC上的NKG 2D受体与角质形成细胞上的MHC I类NKG 2D配体的相互作用激活DETC，然后DETC分泌促进伤口修复的细胞因子。然而，没有直接证据表明DETC通过NKG 2D信号传导激活促进伤口修复。在本研究中，我们生成了先前建议在皮肤角质形成细胞上特异性表达的NKG 2D配体H60 c的mAb。局部施用H60 c特异性mAb抑制DETC的活化并显著延迟伤口修复。同样，NKG 2D特异性mAb给药对伤口修复的损害程度相似。NKG 2D通路阻断导致的伤口闭合延迟与γ δ T细胞缺陷小鼠中观察到的结果相当。这些结果表明，H60 c/NKG 2D相互作用在伤口修复中起关键作用。结合亲和力的重新评估显示，H60 c单体与NKG 2D的结合亲和力（Kd = 26 +/- 3.2 nM）与其他高亲和力NKG 2D配体相当。H60 c不仅在皮肤中转录，而且在已知含有表达不变TCR的上皮驻留γ δ T细胞的组织如舌和女性生殖道中转录，这表明H60 c在维持上皮完整性中具有更普遍的作用。免疫学杂志，2012，188：3972-3979。
Dendritic epidermal T cells (DETCs) found in mouse skin are NKG2D-positive gamma delta T cells involved in immune surveillance and wound repair. It is assumed that the interaction of an NKG2D receptor on DETCs and an MHC class I-like NKG2D ligand on keratinocytes activates DETCs, which then secrete cytokines promoting wound repair. However, direct evidence that DETC activation through NKG2D signaling promotes wound repair is not available. In the present study, we generated mAbs for an NKG2D ligand H60c previously suggested to be expressed specifically on skin keratinocytes. Local administration of H60c-specific mAb inhibited activation of DETCs and significantly delayed wound repair. Likewise, administration of NKG2D-specific mAb impaired wound repair to a similar extent. The delay in wound closure resulting from the blockade of the NKG2D pathway was comparable to that observed in gamma delta T cell-deficient mice. These results indicate that H60c/NKG2D interactions play a critical role in wound repair. Reassessment of binding affinities showed that H60c monomers bind to NKG2D with affinity (K-d = 26 +/- 3.2 nM) comparable to those of other high-affinity NKG2D ligands. H60c is transcribed not only in skin but also in tissues such as tongue and female reproductive tract known to contain epithelium-resident gamma delta T cells expressing invariant TCRs, suggesting a more general role for H60c in the maintenance of epithelial integrity. The Journal of Immunology, 2012, 188: 3972-3979.