Endogenous Regulatory T Cells Adhere in Inflamed Dermal Vessels via ICAM-1: Association with Regulation of Effector Leukocyte Adhesion
Endogenous Regulatory T Cells Adhere in Inflamed Dermal Vessels via ICAM-1: Association with Regulation of Effector Leukocyte Adhesion
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DOI：
10.4049/jimmunol.1102752
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发表时间：
2012-03-01
影响因子：
4.4
通讯作者：
Hickey, Michael J.
中科院分区：
文献类型：
--
作者：
Deane, James A.;Abeynaike, Latasha D.;Hickey, Michael J.
调节性T细胞（TCFs）必须表达适当的皮肤归巢粘附分子，以发挥对皮肤炎症的抑制作用。然而，它们控制局部炎症的机制仍不清楚。在这项研究中，我们在野生型和Foxp 3-GFP小鼠中使用共聚焦活体显微镜来检查效应T细胞和TCFs在真皮小静脉中的粘附。这些实验检查了接触敏感性（CS）的两次激发模型，其中皮肤中的Treg丰度在响应过程中逐渐增加。在CS期间，CD 4（+）T细胞的粘附增加，在初始半抗原攻击后8-24 h达到峰值，并在第二次攻击后4 h内达到峰值。在这些时间点，40%的粘附CD 4（+）T细胞是Foxp 3（+）T细胞。CD 4（+）T细胞粘附高度依赖于ICAM-1，并且与该发现一致，抗ICAM-1阻止Treg粘附。在两次挑战期间，皮肤中的皮肤TGF-β水平升高，与Treg粘附平行。在两次激发的CS模型中，ICAM-1的抑制消除了Treg粘附，这是一种与中性粒细胞粘附显著增加相关的效应。同样，总CD 4（+）T细胞耗竭导致CD 8（+）T细胞粘附增加。由于Treg粘附受到这两种治疗的限制，因此这些实验表明粘附的Treg可以控制体内促炎性白细胞的粘附。此外，ICAM-1在Treg粘附中的关键作用为ICAM-1缺陷小鼠的一些研究中报道的炎症恶化提供了潜在的解释。免疫学杂志，2012，188：2179-2188。
Regulatory T cells (Tregs) must express appropriate skin-homing adhesion molecules to exert suppressive effects on dermal inflammation. However, the mechanisms whereby they control local inflammation remain unclear. In this study we used confocal intravital microscopy in wild-type and Foxp3-GFP mice to examine adhesion of effector T cells and Tregs in dermal venules. These experiments examined a two-challenge model of contact sensitivity (CS) in which Treg abundance in the skin progressively increases during the course of the response. Adhesion of CD4(+) T cells increased during CS, peaking 8-24 h after an initial hapten challenge, and within 4 h of a second challenge. At these time points, 40% of adherent CD4(+) T cells were Foxp3(+) Tregs. CD4(+) T cell adhesion was highly dependent on ICAM-1, and consistent with this finding, anti-ICAM-1 prevented Treg adhesion. Skin TGF-beta levels were elevated in skin during both challenges, in parallel with Treg adhesion. In the two-challenge CS model, inhibition of ICAM-1 eliminated Treg adhesion, an effect associated with a significant increase in neutrophil adhesion. Similarly, total CD4(+) T cell depletion caused an increase in adhesion of CD8(+) T cells. Because Treg adhesion was restricted by both of these treatments, these experiments suggest that adherent Tregs can control adhesion of proinflammatory leukocytes in vivo. Moreover, the critical role of ICAM-1 in Treg adhesion provides a potential explanation for the exacerbation of inflammation reported in some studies of ICAM-1-deficient mice. The Journal of Immunology, 2012, 188: 2179-2188.