Interferon lambda-1 (IFN-lambda1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-lambda1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-lambda-R1/IL-28Ralpha) and CRF2-4 (IL10-R-beta) chains. Like their close relatives, the Type-I interferons, IFN-lambda1, 2 and 3, promote the phosphorylation of STAT1 and STAT2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit antiviral activity in vitro. Their use of the IL10-R-beta chain and their ability to phosphorylate STAT3, STAT4 and STAT5 suggested that they may also exhibit immunomodulatory activity; their antiviral action led us to hypothesize that this activity might be directed toward the Th1/Th2 system. Here, we have demonstrated that IFN-lambda1 altered the activity of Th cells in three separate experimental systems: (i) mitogen stimulation, (ii) mixed-lymphocyte reaction (MLR) and (iii) stimulation of naive T cells by monocyte-derived dendritic cells (mDC). In Con-A stimulation assays, the inclusion of IFN-lambda1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-gamma. IL-13 secretion was 100-fold more sensitive to IFN-lambda1 than was IFN-gamma secretion. These observations were also made in the allogeneic two-way MLR. IFN-lambda1 was able to alter cytokine-mediated Th biasing and when naive T cells were exposed to allogeneic mDC that had been matured in the presence of IFN-lambda1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-gamma was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-lambda1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

中文翻译：

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人干扰素λ-1（IFN-lambda1 / IL-29）调节Th1 / Th2反应。

干扰素lambda-1（IFN-lambda1 / IL-29）是III型干扰素家族的成员，它包含三个配体：IFN-lambda1、2和3。这三个配体使用由CRF2-组成的同一独特的异二聚体受体12条（IFN-λ-R1/ IL-28Ralpha）和CRF2-4（IL10-R-beta）链。像他们的近亲一样，I型干扰素IFN-lambda1、2和3促进STAT1和STAT2的磷酸化，诱导ISRE3复合体，提高OAS和MxA的表达并在体外表现出抗病毒活性。他们使用IL10-R-β链以及磷酸化STAT3，STAT4和STAT5的能力表明它们也可能表现出免疫调节活性。他们的抗病毒作用使我们假设这种活性可能是针对Th1 / Th2系统的。这里，我们已经证明，IFN-lambda1在三个独立的实验系统中改变了Th细胞的活性：（i）促分裂原刺激，（ii）混合淋巴细胞反应（MLR）和（iii）单核细胞衍生的树突状细胞刺激幼稚T细胞（mDC）。在Con-A刺激试验中，包含IFN-lambda1始终导致分泌白介素（IL-13）的水平显着降低，而分泌的IFN-γ偶尔会适度升高。IL-13分泌对IFN-lambda1的敏感性是IFN-γ分泌的100倍。这些观察也是在同种异体双向MLR中进行的。IFN-lambda1能够改变细胞因子介导的Th偏向，当幼稚T细胞暴露于在IFN-lambda1存在下已成熟的同种异体mDC时，分泌的IL-13再次显着且持续降低，而分泌的IFN-γ基本不变。这些功能独立于IL-10。我们的数据支持IFN-lambda1迄今为止在调节Th1和Th2细胞发育中发挥了前所未有的作用，并明显强调了IL-13分泌的减少。