Megjugorac Nicholas J, Gallagher Grant E, Gallagher Grant
Genetic Immunology Laboratory, HUMIGEN LLC, Institute for Genetic Immunology, Hamilton, New Jersey 08690, USA.
J Leukoc Biol. 2009 Dec;86(6):1359-63. doi: 10.1189/jlb.0509347. Epub 2009 Sep 16.
The type III family of IFNs displays immunomodulatory and antiviral activity. Each member (IFN-lambda1, -2, and -3) signals through the same heterodimeric receptor complex, which consists of the binding and signaling subunit (IL-28Ralpha) plus the IL-10Rbeta chain. Although the receptor has a wide tissue distribution, the direct effects of IFN-lambda on various immune cell subsets have not been fully characterized. We have identified high levels of IL-28Ralpha mRNA in pDC from peripheral blood and hypothesized that IFN-lambda plays an important role in pDC maturation and development. We show that stimulation of pDC with HSV or Imiquimod causes an increase in IL-28Ralpha mRNA. In these cells, IFN-lambda1 alters expression of the costimulatory molecules CD80 and ICOS-L and synergizes with IFN-alpha to up-regulate CD83. In addition, IFN-lambda1 has a variable effect on the homing molecule expression of pDC and mDC. IFN-lambda1-treated pDC display a marked difference in their ability to stimulate production of the signature cytokines IL-13, IFN-gamma, and IL-10 in a MLR. This work characterizes the variable effects of IFN-lambda on DC surface molecule expression and identifies a role in pDC activation and immunostimulatory potential.
III型干扰素家族具有免疫调节和抗病毒活性。每个成员（干扰素λ1、λ2和λ3）通过相同的异二聚体受体复合物发出信号，该复合物由结合和信号亚基（IL-28Rα）加上IL-10Rβ链组成。尽管该受体具有广泛的组织分布，但干扰素λ对各种免疫细胞亚群的直接作用尚未完全明确。我们在外周血浆细胞样树突状细胞（pDC）中发现了高水平的IL-28Rα mRNA，并推测干扰素λ在pDC的成熟和发育中起重要作用。我们发现，用单纯疱疹病毒（HSV）或咪喹莫特刺激pDC会导致IL-28Rα mRNA增加。在这些细胞中，干扰素λ1会改变共刺激分子CD80和诱导性共刺激分子配体（ICOS-L）的表达，并与干扰素α协同上调CD83。此外，干扰素λ1对pDC和髓样树突状细胞（mDC）的归巢分子表达有不同影响。经干扰素λ1处理的pDC在混合淋巴细胞反应（MLR）中刺激标志性细胞因子白细胞介素-13（IL-13）、干扰素-γ（IFN-γ）和白细胞介素-10（IL-10）产生的能力存在显著差异。这项研究描述了干扰素λ对树突状细胞表面分子表达的不同影响，并确定了其在pDC激活和免疫刺激潜力方面的作用。
