The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform

V Pekarek - One of the best experts on this subject based on the ideXlab platform.

  • Human Interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response
    Genes & Immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant Gallagher
    Abstract:

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

  • Human Interferon Lambda-1 (IFN-λ1 / IL-29) modulates the Th1/Th2 response. (95.20)
    Journal of Immunology, 2007
    Co-Authors: Grant Gallagher, Joyce Eskdale, S Srinivas, William S. Jordan, V Pekarek
    Abstract:

    Interferon lambda one ((IFN-λ1, IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These ligands use the same hererodimeric receptor, comprised of the CRF2-12 (IFN-λ1/IL-28Rα) chain and the CRF2-4 (IL-10Rβ) chains. Like their close relatives the Type-I Interferons, IFN-λ1, 2 and 3 promote the phosphorylation of STATs 1&2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit anti-viral activity in vitro . Their use of the IL-10Rβ chain and their ability to phospohrylate STATs 3, 4 & 5 suggested that they might also exhibit immunoregulatory activity; their antiviral activity led us to hypothesize that this might be directed towards the Th1/Th2 system. Here, we demonstrate that IFN-λ1 altered the activity of human Th cells in three experimental systems: mitogen stimulation, MLR and the stimulation of naive T-cells by monocyte-derived dendritic cells(mDC). In general the inclusion of IFN-λ1 consistently led to a marked diminution of secreted IL-13 (15/16 donors) with occasional (5/16 donors) coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. IFN-λ1 was able to alter Th-biasing and when naive T-cells were exposed to allogeneic mDC that had been developed in the presence of IFN-λ1, secreted IL-13 was again markedly and consistently reduced. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion in human in vitro cell culture.

  • Human Interferon lambda-1 (IFN- λ 1/IL-29) modulates the Th1/Th2 response
    Genes and immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant E. Gallagher
    Abstract:

    Interferon lambda-1 (IFN-λ1/IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-λ-R1/IL-28Rα) and CRF2-4 (IL10-R-β) chains. Like their close relatives, the Type-I Interferons, IFN-λ1, 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-β 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-λ1 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-λ1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. These observations were also made in the allogeneic two-way MLR. IFN-λ1 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-λ1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-γ was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

Grant Gallagher - One of the best experts on this subject based on the ideXlab platform.

  • Human Interferon Lambda-1 (IFN-λ1 / IL-29) modulates the Th1/Th2 response. (95.20)
    Journal of Immunology, 2007
    Co-Authors: Grant Gallagher, Joyce Eskdale, S Srinivas, William S. Jordan, V Pekarek
    Abstract:

    Interferon lambda one ((IFN-λ1, IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These ligands use the same hererodimeric receptor, comprised of the CRF2-12 (IFN-λ1/IL-28Rα) chain and the CRF2-4 (IL-10Rβ) chains. Like their close relatives the Type-I Interferons, IFN-λ1, 2 and 3 promote the phosphorylation of STATs 1&2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit anti-viral activity in vitro . Their use of the IL-10Rβ chain and their ability to phospohrylate STATs 3, 4 & 5 suggested that they might also exhibit immunoregulatory activity; their antiviral activity led us to hypothesize that this might be directed towards the Th1/Th2 system. Here, we demonstrate that IFN-λ1 altered the activity of human Th cells in three experimental systems: mitogen stimulation, MLR and the stimulation of naive T-cells by monocyte-derived dendritic cells(mDC). In general the inclusion of IFN-λ1 consistently led to a marked diminution of secreted IL-13 (15/16 donors) with occasional (5/16 donors) coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. IFN-λ1 was able to alter Th-biasing and when naive T-cells were exposed to allogeneic mDC that had been developed in the presence of IFN-λ1, secreted IL-13 was again markedly and consistently reduced. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion in human in vitro cell culture.

  • Human Interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response
    Genes & Immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant Gallagher
    Abstract:

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

Joyce Eskdale - One of the best experts on this subject based on the ideXlab platform.

  • Human Interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response
    Genes & Immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant Gallagher
    Abstract:

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

  • Human Interferon Lambda-1 (IFN-λ1 / IL-29) modulates the Th1/Th2 response. (95.20)
    Journal of Immunology, 2007
    Co-Authors: Grant Gallagher, Joyce Eskdale, S Srinivas, William S. Jordan, V Pekarek
    Abstract:

    Interferon lambda one ((IFN-λ1, IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These ligands use the same hererodimeric receptor, comprised of the CRF2-12 (IFN-λ1/IL-28Rα) chain and the CRF2-4 (IL-10Rβ) chains. Like their close relatives the Type-I Interferons, IFN-λ1, 2 and 3 promote the phosphorylation of STATs 1&2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit anti-viral activity in vitro . Their use of the IL-10Rβ chain and their ability to phospohrylate STATs 3, 4 & 5 suggested that they might also exhibit immunoregulatory activity; their antiviral activity led us to hypothesize that this might be directed towards the Th1/Th2 system. Here, we demonstrate that IFN-λ1 altered the activity of human Th cells in three experimental systems: mitogen stimulation, MLR and the stimulation of naive T-cells by monocyte-derived dendritic cells(mDC). In general the inclusion of IFN-λ1 consistently led to a marked diminution of secreted IL-13 (15/16 donors) with occasional (5/16 donors) coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. IFN-λ1 was able to alter Th-biasing and when naive T-cells were exposed to allogeneic mDC that had been developed in the presence of IFN-λ1, secreted IL-13 was again markedly and consistently reduced. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion in human in vitro cell culture.

  • Human Interferon lambda-1 (IFN- λ 1/IL-29) modulates the Th1/Th2 response
    Genes and immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant E. Gallagher
    Abstract:

    Interferon lambda-1 (IFN-λ1/IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-λ-R1/IL-28Rα) and CRF2-4 (IL10-R-β) chains. Like their close relatives, the Type-I Interferons, IFN-λ1, 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-β 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-λ1 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-λ1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. These observations were also made in the allogeneic two-way MLR. IFN-λ1 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-λ1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-γ was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

S Srinivas - One of the best experts on this subject based on the ideXlab platform.

  • Human Interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response
    Genes & Immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant Gallagher
    Abstract:

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

  • Human Interferon Lambda-1 (IFN-λ1 / IL-29) modulates the Th1/Th2 response. (95.20)
    Journal of Immunology, 2007
    Co-Authors: Grant Gallagher, Joyce Eskdale, S Srinivas, William S. Jordan, V Pekarek
    Abstract:

    Interferon lambda one ((IFN-λ1, IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These ligands use the same hererodimeric receptor, comprised of the CRF2-12 (IFN-λ1/IL-28Rα) chain and the CRF2-4 (IL-10Rβ) chains. Like their close relatives the Type-I Interferons, IFN-λ1, 2 and 3 promote the phosphorylation of STATs 1&2, induce the ISRE3 complex, elevate OAS and MxA expression and exhibit anti-viral activity in vitro . Their use of the IL-10Rβ chain and their ability to phospohrylate STATs 3, 4 & 5 suggested that they might also exhibit immunoregulatory activity; their antiviral activity led us to hypothesize that this might be directed towards the Th1/Th2 system. Here, we demonstrate that IFN-λ1 altered the activity of human Th cells in three experimental systems: mitogen stimulation, MLR and the stimulation of naive T-cells by monocyte-derived dendritic cells(mDC). In general the inclusion of IFN-λ1 consistently led to a marked diminution of secreted IL-13 (15/16 donors) with occasional (5/16 donors) coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. IFN-λ1 was able to alter Th-biasing and when naive T-cells were exposed to allogeneic mDC that had been developed in the presence of IFN-λ1, secreted IL-13 was again markedly and consistently reduced. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion in human in vitro cell culture.

  • Human Interferon lambda-1 (IFN- λ 1/IL-29) modulates the Th1/Th2 response
    Genes and immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant E. Gallagher
    Abstract:

    Interferon lambda-1 (IFN-λ1/IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-λ-R1/IL-28Rα) and CRF2-4 (IL10-R-β) chains. Like their close relatives, the Type-I Interferons, IFN-λ1, 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-β 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-λ1 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-λ1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. These observations were also made in the allogeneic two-way MLR. IFN-λ1 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-λ1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-γ was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.

W J Jordan - One of the best experts on this subject based on the ideXlab platform.

  • Human Interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response
    Genes & Immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant Gallagher
    Abstract:

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

  • Human Interferon lambda-1 (IFN- λ 1/IL-29) modulates the Th1/Th2 response
    Genes and immunity, 2007
    Co-Authors: W J Jordan, Joyce Eskdale, S Srinivas, V Pekarek, D Kelner, M Rodia, Grant E. Gallagher
    Abstract:

    Interferon lambda-1 (IFN-λ1/IL-29) is a member of the Type-III Interferon Family, which contains three ligands: IFN-λ1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-λ-R1/IL-28Rα) and CRF2-4 (IL10-R-β) chains. Like their close relatives, the Type-I Interferons, IFN-λ1, 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-β 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-λ1 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-λ1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-γ. IL-13 secretion was 100-fold more sensitive to IFN-λ1 than was IFN-γ secretion. These observations were also made in the allogeneic two-way MLR. IFN-λ1 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-λ1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-γ was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-λ1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.