IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells.

Details

Serval ID
serval:BIB_2C343E244C18
Type
Article: article from journal or magazin.
Collection
Publications
Title
IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Guenova E., Skabytska Y., Hoetzenecker W., Weindl G., Sauer K., Tham M., Kim K.W., Park J.H., Seo J.H., Ignatova D., Cozzio A., Levesque M.P., Volz T., Köberle M., Kaesler S., Thomas P., Mailhammer R., Ghoreschi K., Schäkel K., Amarov B., Eichner M., Schaller M., Clark R.A., Röcken M., Biedermann T.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
17/02/2015
Peer-reviewed
Oui
Volume
112
Number
7
Pages
2163-2168
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Interleukin 4 (IL-4) can suppress delayed-type hypersensitivity reactions (DTHRs), including organ-specific autoimmune diseases in mice and humans. Despite the broadly documented antiinflammatory effect of IL-4, the underlying mode of action remains incompletely understood, as IL-4 also promotes IL-12 production by dendritic cells (DCs) and IFN-γ-producing T(H)1 cells in vivo. Studying the impact of IL-4 on the polarization of human and mouse DCs, we found that IL-4 exerts opposing effects on the production of either IL-12 or IL-23. While promoting IL-12-producing capacity of DCs, IL-4 completely abrogates IL-23. Bone marrow chimeras proved that IL-4-mediated suppression of DTHRs relies on the signal transducer and activator of transcription 6 (STAT6)-dependent abrogation of IL-23 in antigen-presenting cells. Moreover, IL-4 therapy attenuated DTHRs by STAT6- and activating transcription factor 3 (ATF3)-dependent suppression of the IL-23/T(H)17 responses despite simultaneous enhancement of IL-12/TH1 responses. As IL-4 therapy also improves psoriasis in humans and suppresses IL-23/T(H)17 responses without blocking IL-12/T(H)1, selective IL-4-mediated IL-23/T(H)17 silencing is promising as treatment against harmful inflammation, while sparing the IL-12-dependent T(H)1 responses.
Keywords
Antigen-Presenting Cells/immunology, Gene Silencing, Humans, Inflammation/physiopathology, Interleukin-23/genetics, Interleukin-4/physiology, Th17 Cells/immunology, IL-23, IL-4, TH17, dendritic cells, psoriasis
Pubmed
Web of science
Open Access
Yes
Create date
27/08/2020 13:59
Last modification date
02/09/2020 5:26
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