Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Genome and Systems Biology Degree Program, College of Life Science, National Taiwan University, Taipei, Taiwan.
Cell Mol Life Sci. 2024 May 23;81(1):231. doi: 10.1007/s00018-024-05268-2.
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.
CD200 是一种抗炎蛋白，通过其受体 CD200R 在细胞中进行信号转导，从而抑制免疫反应。这包括减少 M1 样巨噬细胞，增强 M2 样巨噬细胞，抑制 NK 细胞细胞毒性，并下调 CTL 反应。已经发现 CD200R 的激活可以调节树突状细胞，导致表达 Foxp3 的 Treg 细胞的诱导或增强。然而，这一过程的确切机制尚不清楚。我们之前的研究表明，派尔氏结中的 B 细胞可以通过 STAT6 磷酸化诱导 Treg 细胞，即所谓的 P 细胞来源的 Treg 细胞（Treg-of-B(P)细胞）。本研究旨在探讨 CD200 在 Treg-of-B(P)细胞生成中的作用。为了阐明机制，我们使用野生型、STAT6 缺陷型和 IL-24 缺陷型 T 细胞生成 Treg-of-B(P)细胞，并使用拮抗剂抗体（抗-CD200 和抗-IL-20RB）、激动型抗-CD200R 抗体、CD39 抑制剂（ARL67156 和 POM-1）、STAT6 抑制剂（AS1517499）和可溶性 IL-20RB。我们的研究结果表明，派尔氏结 B 细胞表达 CD200 以激活 T 细胞上的 CD200R，并启动 Treg-of-B(P)细胞生成过程。CD200 和 CD200R 的相互作用触发 STAT6 的磷酸化，调节 T 细胞中 CD200R、CD39 和 IL-24 的表达。CD39 调节 IL-24 的表达，维持 CD223 和 IL-10 的表达并维持细胞活力。总之，派尔氏结 B 细胞通过 CD200R-STAT6-CD39-IL-24 轴途径生成 Treg-of-B(P)细胞。
