皮内の制御性Ｔ細胞による皮膚免疫応答制御機構の解明

阐明皮内调节性T细胞控制皮肤免疫反应的机制

基本信息

批准号：
18F18096
负责人：
椛島健治
金额：
$ 1.47万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2018
资助国家：
日本
起止时间：
2018-04-25 至 2020-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18F18096/
关键词：
メラノサイト白斑神経 Regulatory T Cell Two photon microscopy Contact Hypersensitivity Dermal dendritic cell iSALT Regulatory T cell Skin inflammation Contact hypersensitivity 三次リンパ組織

项目摘要

The purpose of this research is to further understand regulatory T cell (Tregs) function in the skin during steady state and inflammatory conditions. Briefly, Treg behavior was visualized via a two-photon microscope in the ear skin of a live mouse using various Treg-specific fluorescent reporter mice during the contact hypersensitivity skin inflammatory response. Treg colocalization and interactions with dermal dendritic cells (DCs) was investigated via immunohistochemistry, and the combination of Treg and DC reporter mice.The Treg-Cre recombinase mouse (Foxp3-Cre) was also crossed with a R26-LSL-Gi-DREADD mouse to enable chemical inactivation of chemokine signaling to inhibit Treg migration in the skin. However issues with stochastic activity in the Foxp3-Cre mouse rendered the newly generated mouse unreliable as Gi-DREADD insertion was no longer Treg specific.While studying the relationship between sensory nerves and the immune system, we made a novel observation that chemical denervation with resiniferatoxin (RTX) induced hair loss in mice. Subsequent regrown hair in these bald areas were permenantly pigmented, suggesting a dysfunction in melanocyte stem cells of the affected hair follicles. As Tregs are known to reside around the hair follicle and support hair follicle cycling, we depleted Tregs prior to and during RTX-administration. Surprisingly, Treg-depleted mice had delayed hair regrowth, but regrown hair was still depigmented. This suggests that while Tregs may be important for hair follicle stem cells, they do not affect melanocyte stem cells in the follicle.

这项研究的目的是在稳态和炎症条件下进一步了解皮肤中的调节T细胞（Tregs）功能。简而言之，在接触性超敏性皮肤炎症反应期间，使用各种Treg特异性荧光记者小鼠使用各种Treg特异性荧光记者小鼠通过两光片显微镜观察到Treg行为。通过免疫组织化学研究了TREG共定位和与真皮树突状细胞（DC）的相互作用，并与Treg和DC报告基因小鼠的组合结合。TREG-CRE重组酶小鼠（FOXP3-CRE）也用R26-LSL-GI-DREDD小鼠启用化学化学的化学对化学物质的化学构成对化学物质的化学作用。然而，由于gi-dreadd插入不再是特雷格（Treg）的特异性，因此在FOXP3-CRE小鼠中的随机活性问题使新产生的小鼠不可靠。在研究感觉神经与免疫系统之间的关系时，我们做出了一种新颖的观察结果，即与树脂毒素（RTX）诱导的小鼠脱发的化学神经化作用。随后在这些秃头区域重新生长的头发被有效地着色，表明受影响毛囊的黑素细胞干细胞功能障碍。由于已知Treg驻留在毛囊周围并支持毛囊循环，因此我们在RTX-Administration之前和期间耗尽了Treg。出人意料的是，耗尽的小鼠延迟了头发再生，但头发仍然被脱发。这表明虽然Tregs对毛囊干细胞可能很重要，但它们不会影响卵泡中的黑素细胞干细胞。