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Egr-2 transcription factor is required for Blimp-1 mediated IL-10 production in IL-27 stimulated CD4(+) T cells.
MedLine Citation:
PMID:  23349024     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Interleukin-27 (IL-27) suppresses immune responses through inhibition of the development of IL-17 producing T-helper (Th) 17 cells and induction of IL-10 production. We previously showed that forced expression of early growth response gene 2 (Egr-2), a transcription factor required for T-cell anergy induction, induces IL-10 and lymphocyte activation gene 3 (LAG-3) expression and confers regulatory activity on CD4(+) T cells in vivo. Here we evaluated the role of Egr-2 in IL-27-induced IL-10 production. Among various IL-10-inducing factors, only IL-27 induced high levels of Egr-2 and LAG-3 expression. Intriguingly, IL-27 failed to induce IL-10 in Egr-2-deficient T cells. IL-27-mediated induction of Prdm1 that codes Blimp-1, a transcriptional regulator important for IL-10 production in CD4(+) T cells, was also impaired in the absence of Egr-2. Although IL-27-mediated IL-10 induction was dependent on both STAT1 and STAT3, only STAT3 was required for IL-27-mediated Egr-2 induction. These results suggest that IL-27 signal transduction through Egr-2 and Blimp-1 plays an important role in IL-10 production. Furthermore, Egr-2-deficient CD4(+) T cells showed dysregulated production of IFN-γ and IL-17 in response to IL-27 stimulation. Therefore, Egr-2 may play key roles in controlling the balance between regulatory and effector cytokines.
Authors:
Yukiko Iwasaki; Keishi Fujio; Tomohisa Okamura; Atsushi Yanai; Shuji Sumitomo; Hirofumi Shoda; Tomohiko Tamura; Hiroki Yoshida; Patrick Charnay; Kazuhiko Yamamoto
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-25
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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