School of Veterinary Medicine and Science, University of Nottingham, UK.
Eur J Immunol. 2012 Mar;42(3):607-17. doi: 10.1002/eji.201142035.
We report for the first time that expression of the novel IL-1 cytokine receptor IL-1Rrp2 (IL-1R6) is unique to DCs within the human myelomonocytic lineage. IL-1Rrp2 was expressed by monocyte-derived dendritic cells (MDDCs) which was dose-dependently increased by IL-4 and correlated with increased numbers of differentiated MDDCs. Human plasmacytoid DCs also express IL-1Rrp2 but the receptor is not expressed by either myeloid DC type 1 (mDC1) or mDC2 cells. We also show that IL-1F8 or IL-1F9 cytokines, which signal through IL-1Rrp2, induce maturation of MDDCs, as measured by increased expression of HLA-DR and CD83 and decreased expression of CD1a. Furthermore, IL-1F8 stimulated increased CD40 and CD80 expression and IL-18 and IL-12 p70 production by MDDCs, which induced proliferation of IFN-γ-producing CD3(+) lymphocytes (indicative of inflammatory Th1 subsets). IL-1F8 and IL-1F2 were equipotent in their ability to stimulate IL-18 secretion from MDDCs but IL-1F8 was not as potent as IL-1F2 in stimulating secretion of IL-12p70 from MDDCs or inducing lymphocyte proliferation Therefore, IL-1Rrp2 expression by some DC subsets may have an important function in the human immune response in vivo via its role in differentiation of inflammatory Th1 lymphocytes.
我们首次报道，新型白细胞介素-1 细胞因子受体 IL-1Rrp2（IL-1R6）的表达在人类骨髓单核细胞谱系中的 DC 中是独特的。IL-1Rrp2 由单核细胞衍生的树突状细胞（MDDC）表达，其表达量随 IL-4 的剂量依赖性增加，并与分化的 MDDC 数量增加相关。人浆细胞样 DC 也表达 IL-1Rrp2，但该受体不表达于骨髓树突状细胞 1 型（mDC1）或 mDC2 细胞。我们还表明，白细胞介素-1F8 或白细胞介素-1F9 细胞因子通过 IL-1Rrp2 信号传导，诱导 MDDC 的成熟，如 HLA-DR 和 CD83 的表达增加以及 CD1a 的表达减少所测量的。此外，IL-1F8 刺激 MDDC 表达增加 CD40 和 CD80 的表达以及 IL-18 和 IL-12p70 的产生，诱导 IFN-γ 产生的 CD3(+)淋巴细胞增殖（表明炎症性 Th1 亚群）。IL-1F8 和 IL-1F2 刺激 MDDC 分泌 IL-18 的能力相当，但 IL-1F8 刺激 MDDC 分泌 IL-12p70 或诱导淋巴细胞增殖的能力不如 IL-1F2 强。因此，某些 DC 亚群的 IL-1Rrp2 表达可能通过其在炎症性 Th1 淋巴细胞分化中的作用在体内的人类免疫反应中具有重要功能。
