Interferon-λ1 (interleukin-29) preferentially down-regulates interleukin-13 over other T helper type 2 cytokine responses in vitro
Version of Record online: 10 JUN 2008
© 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd
Volume 125, Issue 4, pages 492–502, December 2008
How to Cite
Srinivas, S., Dai, J., Eskdale, J., Gallagher, G. E., Megjugorac, N. J. and Gallagher, G. (2008), Interferon-λ1 (interleukin-29) preferentially down-regulates interleukin-13 over other T helper type 2 cytokine responses in vitro. Immunology, 125: 492–502. doi: 10.1111/j.1365-2567.2008.02862.x
- Issue online: 5 NOV 2008
- Version of Record online: 10 JUN 2008
- Received 1 January 2008; revised 26 March, 7 April 2008; accepted 8 April 2008.
- T helper type 2
Interferon (IFN)-λ1 [interleukin (IL)-29] is a member of the interferon lambda family (also known as type III interferons), whose members are distantly related to both the type I interferons and members of the IL-10 family. While IFN-λ1 has significant antiviral activity, it is also becoming apparent that it has important immunoregulatory properties, especially with regard to the T helper type 2 (Th2) response. Previously, we have shown that IFN-λ1 is capable of down-regulating IL-13 production in an IFN-γ-independent manner and that this is mediated in part via monocyte-derived dendritic cells. Here, we have extended our knowledge of IFN-λ1 regulation of the human in vitro Th2 response by examining the regulation of three major Th2 cytokines, IL-4, IL-5 and IL-13, by IFN-λ1. Our results reveal that IFN-λ1 preferentially inhibits IL-13 production, compared with IL-4 or IL-5. Levels of IL-13 mRNA, the amount of secreted IL-13 protein and numbers of IL-13-positive CD3+ CD4+ cells were all significantly diminished by IFN-λ1. IFN-λ1 significantly decreased some aspects of IL-4 and IL-5 production, but its effects were not as consistent as those seen on IL-13. IFN-λ1 was also effective at decreasing IL-13 secretion under conditions designed to support the generation of Th2 cells. Irrespective of whether Concanavalin-A or T-cell-stimulatory microbeads were used, IFN-λ1 markedly diminished IL-13 secretion in cultures where IL-4 had been added. Thus, IFN-λ1 appears to be an inhibitor of human Th2 responses whose action is primarily directed towards IL-13 but which may also affect Th2 responses generally and does not invoke a complementary elevation of IFN-γ secretion.