Regulation of the development of acute hepatitis by IL-23 through IL-22 and IL-17 production.

Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 1273201 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-4141 (Electronic) Linking ISSN: 00142980 NLM ISO Abbreviation: Eur J Immunol Subsets: MEDLINE

Publication: <2005->: Weinheim : Wiley-VCH
Original Publication: Weinheim, Verlag Chemie GmbH.

Interleukin-23*/administration & dosage ; Interleukin-23*/biosynthesis ; Interleukin-23*/metabolism ; Interleukin-23*/pharmacology; Hepatitis, Animal/*immunology ; Hepatitis, Animal/*metabolism ; Interleukin-17/*metabolism ; Interleukin-23 Subunit p19/*metabolism ; Interleukins/*metabolism; Animals ; Concanavalin A ; Cytokines/biosynthesis ; Interleukin-17/blood ; Interleukin-17/genetics ; Interleukin-23 Subunit p19/genetics ; Interleukins/administration & dosage ; Interleukins/blood ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Aryl Hydrocarbon/metabolism ; Receptors, Notch/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; STAT3 Transcription Factor/metabolism ; STAT4 Transcription Factor/metabolism ; Signal Transduction/drug effects ; Th17 Cells/immunology ; Th17 Cells/metabolism ; Interleukin-22

IL-23 plays a critical role in the expansion of highly proinflammatory Th17 cells secreting IL-17 and IL-22. Recently, we demonstrated that Notch signaling drives IL-22 secretion through the aryl hydrocarbon receptor (AHR) and plays a protective role in Con A-induced hepatitis. In this study, we investigated the role of IL-23 in hepatitis using IL-23p19- and IL-17-deficient mice. In WT mice, the injection of Con A induced the upregulation of various cytokines, which included IL-23, IL-22, IL-17, IFN-γ and TNF-α. In IL-23p19-deficient mice, exacerbated hepatitis was observed and serum IL-22 and IL-17 levels were greatly reduced, whereas in IL-17-deficient mice, ameliorated hepatitis was observed. The injection of exogenous IL-22 protected p19-deficient mice from hepatitis, whereas the injection of exogenous IL-23 significantly increased the serum levels of not only IL-22 but also IL-17, and less effectively protected against hepatitis in IL-17-dependent and -independent manners. Finally, it was revealed that STAT3, STAT4 and Notch contributed to the production of both the cytokines, and that the AHR was important only for IL-22 production in response to Con A and IL-23 in liver mononuclear cells. These results suggest that IL-23 plays a protective role in hepatitis through IL-22 production and also a pathological role via IL-17-dependent and -independent mechanisms.
(Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

0 (Cytokines)
0 (Interleukin-17)
0 (Interleukin-23)
0 (Interleukin-23 Subunit p19)
0 (Interleukins)
0 (Receptors, Aryl Hydrocarbon)
0 (Receptors, Notch)
0 (STAT3 Transcription Factor)
0 (STAT4 Transcription Factor)
0 (Stat3 protein, mouse)
0 (Stat4 protein, mouse)
11028-71-0 (Concanavalin A)

Date Created: 20110929 Date Completed: 20111207 Latest Revision: 20231213

20231215

10.1002/eji.201141291

21953641