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| Status |
Public on Oct 03, 2016 |
| Title |
IL-23 promotes immunopathology and prevents IL-13-dependent tissue repair by Ly6Clo monocytes in parasite-induced liver damage |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background & Aims: The IL-23/IL-17 axis plays an important role in the pathogenesis of autoimmune diseases and the pathological consequences of infection. We previously showed that immunopathologic mechanisms mediated by inflammatory monocytes underlie the severe focal liver damage induced by the protozoan parasite, Entamoeba histolytica. Here, we analyze the contribution of the IL-23/IL-17 axis to the induction and subsequent recovery from parasite-induced liver damage. Methods: IL-23p19-/-, IL-17A/F-/-, CCR2-/-, and WT mice were intra-hepatically infected with E. histolytica trophozoites and disease onset and recovery were analyzed by magnetic resonance imaging. The expression of liver-specific genes and proteins during infection was examined by qPCR, microarray, FACS analysis and immunohistochemistry. Immuno-depletion and substitution experiments were performed in IL-23p19-/- and WT mice to investigate the role of IL-13 in disease outcome. Results: Liver damage in infected IL-23p19-/-, IL-17A/F-/-, CCR2-/- mice was strongly attenuated compared with that in WT mice. IL-23p19-/- mice showed reduced expression of IL-17 and CCL2 genes and proteins. Increased numbers of IL-13-producing CD11b+Ly6Clo regenerative monocytes were associated with disease attenuation in IL-23p19-/- mice. Immuno-depletion of IL-13 in IL-23-/- mice reversed this attenuation and treatment of infected WT mice with an IL-13/anti-IL-13-mAb complex supported liver recovery. Conclusions: The IL-23/IL-17 axis plays a critical role in the immunopathology of hepatic amebiasis. IL- 13 secreted by CD11b+Ly6Clo monocytes supports recovery from liver damage. An IL-13/anti-IL13- mAb complex mimics this function, suggesting a novel therapeutic option to support tissue healing after liver damage.
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| Overall design |
Total liver RNA was extracted from wildtype and IL23-p19-/- mice previously infected intra-hepatically with E. histolytica trophozoites. The material was isolated 0 hours or 6 hours post infection.
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| Contributor(s) |
Noll J, Lotter H, Otto B |
| Citation missing |
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| Submission date |
Oct 02, 2015 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Thomas Streichert |
| Organization name |
University Medical Center Hamburg-Eppendorf
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| Department |
Institute For Clinical Chemistry / Central Laboratories
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| Street address |
Martinistr. 52, Campus Forschung N27, 2. OG
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| City |
Hamburg |
| ZIP/Postal code |
D-20246 |
| Country |
Germany |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA297666 |
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