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Interferon‐λ1 (interleukin‐29) preferentially down‐regulates interleukin‐13 over other T helper type 2 cytokine responses in vitro
Author(s) -
Srinivas Shekar,
Dai Jihong,
Eskdale Joyce,
Gallagher Grant E.,
Megjugorac Nicholas J.,
Gallagher Grant
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02862.x
Subject(s) - biology , interferon , interleukin 4 , cytokine , secretion , concanavalin a , microbiology and biotechnology , in vitro , immunology , biochemistry
Summary 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.