PDF(Pubmed)
Abstract：
CD200 is an anti-inflammatory protein that facilitates signal transduction through its receptor, CD200R, in cells, resulting in immune response suppression. This includes reducing M1-like macrophages, enhancing M2-like macrophages, inhibiting NK cell cytotoxicity, and downregulating CTL responses. Activation of CD200R has been found to modulate dendritic cells, leading to the induction or enhancement of Treg cells expressing Foxp3. However, the precise mechanisms behind this process are still unclear. Our previous study demonstrated that B cells in Peyer\'s patches can induce Treg cells, so-called Treg-of-B (P) cells, through STAT6 phosphorylation. This study aimed to investigate the role of CD200 in Treg-of-B (P) cell generation. To clarify the mechanisms, we used wild-type, STAT6 deficient, and IL-24 deficient T cells to generate Treg-of-B (P) cells, and antagonist antibodies (anti-CD200 and anti-IL-20RB), an agonist anti-CD200R antibody, CD39 inhibitors (ARL67156 and POM-1), a STAT6 inhibitor (AS1517499), and soluble IL-20RB were also applied. Our findings revealed that Peyer\'s patch B cells expressed CD200 to activate the CD200R on T cells and initiate the process of Treg-of-B (P) cells generation. CD200 and CD200R interaction triggers the phosphorylation of STAT6, which regulated the expression of CD200R, CD39, and IL-24 in T cells. CD39 regulated the expression of IL-24, which sustained the expression of CD223 and IL-10 and maintained the cell viability. In summary, the generation of Treg-of-B (P) cells by Peyer\'s patch B cells was through the CD200R-STAT6-CD39-IL-24 axis pathway.
摘要：
CD200是一种抗炎蛋白，通过其受体促进信号转导，CD200R,在细胞中，导致免疫反应抑制。这包括减少M1样巨噬细胞，增强M2样巨噬细胞，抑制NK细胞的细胞毒性，和下调CTL反应。已经发现CD200R的激活调节树突状细胞,导致表达Foxp3的Treg细胞的诱导或增强。然而,这一过程背后的确切机制仍不清楚。我们先前的研究表明，Peyer的斑块中的B细胞可以诱导Treg细胞，所谓的Treg-of-B(P)细胞,通过STAT6磷酸化。本研究旨在探讨CD200在Treg-of-B(P)细胞生成中的作用。为了澄清机制，我们用的是野生型,STAT6不足，和IL-24缺陷的T细胞，以产生Treg-of-B（P）细胞，和拮抗剂抗体（抗CD200和抗IL-20RB），激动剂抗CD200R抗体，CD39抑制剂（ARL67156和POM-1），STAT6抑制剂（AS1517499），和可溶性IL-20RB也被应用。我们的发现表明，Peyer的斑块B细胞表达CD200以激活T细胞上的CD200R并启动Treg-of-B（P）细胞的生成过程。CD200与CD200R相互作用引发STAT6磷酸化，从而调控CD200R的表达，T细胞中的CD39和IL-24。CD39调节IL-24的表达，从而维持CD223和IL-10的表达并维持细胞活力。总之,Peyer's补片B细胞通过CD200R-STAT6-CD39-IL-24轴途径产生Treg-of-B(P)细胞。
