Article

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.

Department of Gastroenterology and Hepatology, Erasmus Medical Center, University Medical Center Rotterdam, 's-Gravendijkwal 230, Rotterdam, The Netherlands.
Blood (impact factor: 9.9). 12/2010; 117(8):2385-95. DOI:10.1182/blood-2010-07-298976 pp.2385-95
Source: PubMed

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.

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Keywords

antigen-presenting cells
 
antiviral activities
 
cytokines
 
human macrophages
 
human monocyte-derived macrophages
 
IFNα down-regulated
 
IFNα suppressed IFNγ-induced IL-12p40
 
IFNγ receptor 1 chain
 
IFNγ-induced IL-12p40
 
IL-10 signaling
 
IL-28 receptor α chain expression
 
IL-29-treated macrophages
 
modulating TLR-induced cytokine production
 
monocyte-derived dendritic cells
 
R848 stimulation
 
regulating immunity
 
TLR)-induced IL-12p40 production
 
TLR-challenged macrophages
 
tumor necrosis factor
 
tumor necrosis factor TNF production