title: IL-29 and IFNα differ in their ability to modulate IL-12 production by TLR-activated human macrophages and exhibit differential regulation of the IFNγ receptor expression.
abstract: The interferon-λ (IFNλ) family of cytokines, consisting of interleukin-28A (IFNλ2), IL-28B (IFNλ3), and IL-29 (IFNλ1), have been extensively studied for their antiviral activities. However, little is known about the effect of IFNλ on antigen-presenting cells. In the present study, we show for the first time that IL-29 can increase Toll-like receptor (TLR)-induced IL-12p40 production by human monocyte-derived macrophages. In contrast, IL-29 did not affect monocytes or monocyte-derived dendritic cells (DCs) because of restricted IL-28 receptor α chain expression by macrophages. Furthermore, IL-29-treated macrophages were more responsive to IFNγ, because IL-29 enhanced IFNγ-induced IL-12p40 and tumor necrosis factor (TNF) production by macrophages on R848 stimulation. However, IFNα suppressed IFNγ-induced IL-12p40 and tumor necrosis factor TNF production by human macrophages. The differential effects of IL-29 and IFNα on the responsiveness of macrophages to IFNγ could not be explained by an effect on TLR7 or TLR8 mRNA expression or by altered IL-10 signaling. However, we demonstrated that IL-29 up-regulated, whereas IFNα down-regulated, the surface expression of the IFNγ receptor 1 chain on macrophages, thereby resulting in differential responsiveness of TLR-challenged macrophages to IFNγ. Our findings on the differences between IFNα and IL-29 in modulating TLR-induced cytokine production by macrophages may contribute to understanding the role of IFNs in regulating immunity to pathogens.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 's-Gravendijkwal 230, Rotterdam, The Netherlands.
authors.forename: Bi-Sheng
authors.initials: BS
authors.lastname: Liu
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007372:Interferons; D018664:Interleukin-12 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40; D007378:Interleukins / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D017471:Receptors, Interferon / Q000235:genetics*; D051193:Toll-Like Receptors / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; D000095022:Interferon Lambda
chemical_list: D016898:Interferon-alpha; D007372:Interferons; D018664:Interleukin-12; D053762:Interleukin-12 Subunit p40; D007378:Interleukins; D017471:Receptors, Interferon; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda