Women's and Children's Health Research Institute, 72 King William Road, North Adelaide, South Australia, 5006, Australia.
Cell Immunol. 2012 Jan-Feb;275(1-2):12-8. doi: 10.1016/j.cellimm.2012.04.002. Epub 2012 Apr 6.
The peptidase inhibitor PI16 was shown previously by microarray analysis to be over-expressed by CD4-positive/CD25-positive Treg compared with CD4-positive/CD25-negative Th cells. Using a monoclonal antibody to the human PI16 protein, we found that PI16-positive Treg have a memory (CD45RO-positive) phenotype and express higher levels of FOXP3 than PI16-negative Treg. PI16-positive Treg are functional in suppressor assays in vitro with potency similar to PI16-negative Treg. Further phenotyping of the PI16-positive Treg revealed that the chemokine receptors CCR4 and CCR6 are expressed by more of the PI16-positive/CD45RO-positive Treg compared with PI16-negative/CD45RO-positive Treg or Th cells. PI16-positive Treg showed enhanced in vitro migration towards the inflammatory chemokines CCL17 and CCL20, suggesting they can migrate to sites of inflammation. We conclude that PI16 identifies a novel distinct subset of functional memory Treg which can migrate to sites of inflammation and regulate the pro-inflammatory response at those sites.
先前的微阵列分析显示，与 CD4阳性/CD25阴性 Th 细胞相比，CD4阳性/CD25阳性 Treg 中肽酶抑制剂 PI16 表达上调。使用针对人 PI16 蛋白的单克隆抗体，我们发现 PI16 阳性 Treg 具有记忆（CD45RO 阳性）表型，并且表达的 FOXP3 水平高于 PI16 阴性 Treg。PI16 阳性 Treg 在体外抑制试验中具有功能，其效力与 PI16 阴性 Treg 相似。对 PI16 阳性 Treg 的进一步表型分析表明，与 PI16 阴性/CD45RO 阳性 Treg 或 Th 细胞相比，趋化因子受体 CCR4 和 CCR6 在更多的 PI16 阳性/CD45RO 阳性 Treg 中表达。PI16 阳性 Treg 显示出对炎症趋化因子 CCL17 和 CCL20 的体外迁移增强，表明它们可以迁移到炎症部位。我们得出结论，PI16 鉴定了一种新型的功能记忆性 Treg 亚群，其可以迁移到炎症部位，并在这些部位调节促炎反应。
