Regulatory T cells (Tregs) are immune regulatory T cells that are vital for controlling inflammation. The role of Tregs in inflammatory diseases namely Psoriatic Arthritis (PsA) is still poorly understood. The underlying reason being a lack of robust unbiased analysis to test the immune regulatory phenotype of human Tregs. Here, we propose that checkpoint receptors can identify functional Tregs in PsA. Using unbiased BD RhapsodyTM single cell analysis, we have analyzed the expression pattern of checkpoint receptors in Tregs and found that PsA Tregs are enriched in the expression of CTLA4, TIGIT, PD-1 and GITR while TIM3 was downregulated. Furthermore, PD-1+ Tregs in PsA had an increased type 1 phenotype and expressed the protease asparaginyl endopeptidase. By harnessing the PD-1 signaling pathway and inhibiting asparaginyl endopeptidase, PsA Treg function was significantly enhanced in in-vitro suppressor assays. Next, we interrogated the cell interaction pathways of Tregs in PsA and found a diminished crosstalk with circulating osteoclast precursors (OCP) through the CD244:CD48 co-receptor pathways. Therapeutically, PsA Treg function could be enhanced by modulating PD-1 and osteoclast interactions. Our study suggests unconventional immune cell crosstalk with Tregs is severely diminished in PsA.

中文翻译：

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银屑病关节炎中 T 调节细胞的深度表型分析突出了疾病的靶向机制。


调节性 T 细胞 （Tregs） 是免疫调节性 T 细胞，对控制炎症至关重要。Tregs 在炎症性疾病中的作用，即银屑病关节炎 （PsA） 仍然知之甚少。根本原因是缺乏稳健的无偏倚分析来测试人类 Tregs 的免疫调节表型。在这里，我们提出检查点受体可以识别 PsA 中的功能性 Tregs。使用无偏倚的 BD RhapsodyTM 单细胞分析，我们分析了 Tregs 中检查点受体的表达模式，发现 PsA Tregs 富含 CTLA4、TIGIT、PD-1 和 GITR 的表达，而 TIM3 下调。此外，PsA 中的 PD-1 + Tregs 具有增加的 1 型表型并表达蛋白酶天冬酰胺内肽酶。通过利用 PD-1 信号通路和抑制天冬酰胺内肽酶，PsA Treg 功能在体外抑制因子测定中得到显着增强。接下来，我们询问了 PsA 中 Tregs 的细胞相互作用通路，发现通过 CD244：CD48 共受体通路与循环破骨细胞前体 （OCP） 的串扰减弱。在治疗上，PsA Treg 功能可以通过调节 PD-1 和破骨细胞相互作用来增强。我们的研究表明，在 PsA 中，非常规免疫细胞与 Tregs 的串扰严重减少。