Human interferon lambda-1 (IFN-lambda1/IL-29) modulates the Th1/Th2 response.
Interferon lambda-1 (IFN-lambda1/IL-29) is a member of the Type-III interferon family, which contains three ligands: IFN-lambda1, 2 and 3. These three ligands use the same unique heterodimeric receptor composed of CRF2-12 (IFN-lambda-R1/IL-28Ralpha) and CRF2-4 (IL10-R-beta) chains. Like their close relatives, the Type-I interferons, IFN-lambda1, 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-beta 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-lambda1 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-lambda1 consistently led to markedly diminished levels of secreted interleukin (IL-13) with occasional coincident, modest elevation of secreted IFN-gamma. IL-13 secretion was 100-fold more sensitive to IFN-lambda1 than was IFN-gamma secretion. These observations were also made in the allogeneic two-way MLR. IFN-lambda1 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-lambda1, secreted IL-13 was again markedly and consistently reduced, whereas secreted IFN-gamma was largely unaltered. These functions were independent of IL-10. Our data support a hitherto unsuspected role for IFN-lambda1 in modulating the development of Th1 and Th2 cells, with an apparent emphasis on the diminution of IL-13 secretion.
Jordan
W J
WJ
Department of Oral Biology, New Jersey Dental School, Newark, NJ, USA.
Eskdale
J
J
Srinivas
S
S
Pekarek
V
V
Kelner
D
D
Rodia
M
M
Gallagher
G
G
D016207:Cytokines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007372:Interferons; D016753:Interleukin-10 / Q000037:antagonists & inhibitors; D018793:Interleukin-13 / Q000096:biosynthesis; D007378:Interleukins / Q000494:pharmacology*; D007519:Isoantigens; D007959:Lymphocyte Culture Test, Mixed; D011994:Recombinant Proteins / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology*; D000095022:Interferon Lambda
D016207:Cytokines; D007371:Interferon-gamma; D007372:Interferons; D016753:Interleukin-10; D018793:Interleukin-13; D007378:Interleukins; D007519:Isoantigens; D011994:Recombinant Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda