CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease.
CCR9 expression defines tolerogenic plasmacytoid dendritic cells able to suppress acute graft-versus-host disease.
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树突状细胞是专职的抗原呈递细胞，在免疫应答的调节中起关键作用。在这里，我们描述了一个独特的致耐受性DC亚群，其表达趋化因子受体CCR9并迁移至CCR9配体CCL25，CCL25是一种与T细胞和DC归巢至肠道有关的趋化因子。CCR9+ DC是浆细胞样DC谱系，具有未成熟表型，并响应于成熟诱导的pDC限制性Toll样受体配体而快速下调CCR9。CCR9+ pDCs是调节性T细胞功能的有效诱导剂，并在体外和体内抑制抗原特异性免疫应答，包括抑制辐射受体中同种异体CD4+供体T细胞诱导的急性移植物抗宿主病。结果鉴定了存在于淋巴组织中的高度免疫抑制的pDC群体。
Dendritic cells are professional antigen-presenting cells that play a key role in the regulation of immune responses. Here we characterize a unique subset of tolerogenic DCs that expressed the chemokine receptor CCR9 and migrated to the CCR9 ligand CCL25, a chemokine implicated in T cell and DC homing to the gut. CCR9+ DCs were of the plasmacytoid DC lineage, possessed an immature phenotype and rapidly downregulated CCR9 in response to maturation-inducing pDC-restricted Toll-like receptor ligands. CCR9+ pDCs were potent inducers of regulatory T cell function and suppressed antigen-specific immune responses both in vitro and in vivo, including inhibition of acute graft-versus-host disease induced by allogeneic CD4+ donor T cells in irradiated recipients. The results identify a highly immunosuppressive population of pDCs present in lymphoid tissues.