Publikation

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

Wissenschaftlicher Artikel/Review - 02.02.2015

Bereiche
PubMed
DOI

Zitation
Guenova E, Kaesler S, Thomas P, Mailhammer R, Ghoreschi K, Schäkel K, Amarov B, Eichner M, Schaller M, Clark R, Röcken M, Köberle M, Volz T, Levesque M, Skabytska Y, Hoetzenecker W, Weindl G, Sauer K, Tham M, Kim K, Park J, Seo J, Desislava I, Cozzio A, Biedermann T. IL-4 abrogates T(H)17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells. Proc Natl Acad Sci USA 2015; 112:2163-8.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Proc Natl Acad Sci USA 2015; 112
Veröffentlichungsdatum
02.02.2015
eISSN (Online)
1091-6490
Seiten
2163-8
Kurzbeschreibung/Zielsetzung

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.