Human Interferon Lambda-1 (IFN-λ1 / IL-29) modulates the Th1/Th2 response. (95.20)

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.