Modulation of the human cytokine response by interferon lambda-1 (IFN-λ1/IL-29)

Jordan, William J.; Eskdale, Joyce; Boniotto, Michele; Rodia, Maria Teresa; Kellner, Daniel B.; Gallagher, Grant

doi:10.1038/sj.gene.6364348

Cited by 118 publications

(105 citation statements)

References 52 publications

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“…We confirmed the broad expression pattern of the IFNAR system, and found that among the cell types examined, that pDCs were the only hemopoietic cell type that responded to IFN-. Others have reported that human monocytes, blood monocyte-derived DCs, and murine intrahepatic CD3 Ϫ DX5 ϩ NK cells respond to IFN-or express the receptor chains (28,29,47,49). Therefore, we conclude that only few cell types of the hemopoietic compartment are responsive to IFN-, although we cannot exclude that expression of the type III IFN receptor system may be induced by cell differentiation and activation in a broader spectrum of cells.…”

Section: Discussioncontrasting

confidence: 53%

“…Accumulating evidence now suggests that IFN-can affect the host response in a broader manner. For instance, treatment with IFN-1 induces expression of a subset of inflammatory cytokines in human monocytes and macrophages (47,48). Others have reported that human blood monocytes gain responsiveness to IFNduring differentiation to DCs, and that these DCs induce proliferation of regulatory T cells (29) and modulation of the Th1/Th2 response (49).…”

Section: Discussionmentioning

confidence: 99%

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An Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral Activity

Ank

Iversen

Bartholdy

et al. 2008

The Journal of Immunology

391

410

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Type III IFNs (IFN-λ/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-λ was restricted to a narrow subset of cells, including plasmacytoid dendritic cells and epithelial cells. To examine the role of type III IFN in antiviral defense, we generated IL-28Rα-deficient mice. These mice were indistinguishable from wild-type mice with respect to clearance of a panel of different viruses, whereas mice lacking the type I IFN receptor (IFNAR−/−) were significantly impaired. However, the strong antiviral activity evoked by treatment of mice with TLR3 or TLR9 agonists was significantly reduced in both IL-28RA−/− and IFNAR−/− mice. The type I IFN receptor system has been shown to mediate positive feedback on IFN-αβ expression, and we found that the type I IFN receptor system also mediates positive feedback on IFN-λ expression, whereas IL-28Rα signaling does not provide feedback on either type I or type III IFN expression in vivo. Finally, using bone-marrow chimeric mice we showed that TLR-activated antiviral defense requires expression of IL-28Rα only on nonhemopoietic cells. In this compartment, epithelial cells responded to IFN-λ and directly restricted virus replication. Our data suggest type III IFN to target a specific subset of cells and to contribute to the antiviral response evoked by TLRs.

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

An Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral Activity

Ank

Iversen

Bartholdy

et al. 2008

The Journal of Immunology

391

410

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“…29 Future studies will be directed towards greater understanding of the immumomodulatory role of IFN-l1 in the human system. It will be of interest to determine which leukocyte populations are most responsive to IFN-l1 regarding CXC ELR À chemokine production (we have shown previously that monocytes are particularly responsive for cytokine secretion 26 ) and to define any cooperative effects between IFN-l1 and IFN-g.…”

Section: Induction Of Elrmentioning

confidence: 99%

“…Eight donors were examined in the present preliminary study. PBMCs were established in culture in the presence or absence of 1000 ng/ml (as described previously by Jordan et al 26 ) human IFN-l1 (Peprotech, Princeton, NJ, USA) over a time course covering 15, 30, 60, 90, 120, 180 and 240 min, and 24, 48 and 72 h. Cells were harvested, total RNA extracted (Qiagen, Valencia, CA, USA) and the levels of MIG, IP-10 and I-TAC mRNA determined by quantitative reverse transcription PCR (Q-RTPCR) relative to the housekeeping gene HPRT. The change in chemokine mRNA levels caused by exposure to IFN-l1 are shown in Figure 1.…”

mentioning

confidence: 99%

Interferon lambda-1 (IFN-λ1/IL-29) induces ELR− CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-γ-independent manner

et al. 2007

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Interferon lambda-1 (IFN-l1), the prototype Type-III interferon, has antiviral functions similar to those of the Type-I interferons, IFN-a and IFN-b. However, IFN-l1 is capable of signaling through almost all STAT molecules and so it is possible that it may have novel immunoregulatory functions in addition to antiviral ones. From a range of chemokines tested, IFN-l1 elevated mRNA levels of only 'Monokine induced by IFN-gamma' (MIG/CXCL9), 'IFN-gamma inducible protein-10' (IP-10/CXCL10) and 'IFN-gamma inducible T-cell a chemoattractant' (I-TAC/CXCL11) from human peripheral blood mononuclear cells. As their names suggest, these chemokines are also induced by IFN-g, the only member of the Type-II interferon family. This action of IFN-l1 did not depend on intermediate induction of IFN-g and is therefore, likely to be independent of IFN-g. Further, our results suggest that donors responded to IFN-l1 stimulation either 'early' or 'late'. Overall the action of IFN-l1 was similar to that previously reported for IFN-g and may invite more detailed investigation of the role of IFN-l1 at the innate/adaptive interface.

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“…We have recently demonstrated that IFN-l1 will elevate IL-10 levels in in vitro cultures of human peripheral blood mononuclear cells (PBMCs) and that endogenous IL-10 can moderate IFN-l1-induced responses. 38 We wished to see whether the ability of IFNl1 to reduce IL-13 secretion was influenced by IL-10. As shown in Figure 2a, the anti-IL-10 antibody elevated the secretion of IL-13, suggesting that endogenous IL-10 in the cultures was controlling IL-13 secretion.…”

Section: Introductionmentioning

confidence: 99%

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

et al. 2007

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Interferon lambda-1 (IFN-l1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-l1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-l-R1/IL-28Ra) and CRF2-4 (IL10-R-b) chains. Like their close relatives, the Type-I interferons, IFN-l1, 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-b 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-l1 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-l1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-g. IL-13 secretion was 100-fold more sensitive to IFN-l1 than was IFN-g secretion. These observations were also made in the allogeneic two-way MLR. IFN-l1 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-l1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-g was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-l1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

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Modulation of the human cytokine response by interferon lambda-1 (IFN-λ1/IL-29)

Cited by 118 publications

References 52 publications

An Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral Activity

An Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral Activity

Interferon lambda-1 (IFN-λ1/IL-29) induces ELR− CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-γ-independent manner

Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response

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