Interleukin-22 but Not Interleukin-17 Provides Protection to Hepatocytes during Acute Liver Inflammation

Zenewicz, Lauren A.; Yancopouloš, George D.; Valenzuela, David M.; Murphy, Andrew J.; Karow, Margaret; Flavell, Richard A.

doi:10.1016/j.immuni.2007.07.023

Cited by 565 publications

(592 citation statements)

References 55 publications

(83 reference statements)

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“…To the best of our knowledge, there are two conflicting reports as to the susceptibility of IL-17-deficient mice to Con A-induced hepatitis [24,31]. Therefore, to further clarify the role of IL-17 in Con A-induced hepatitis, we investigated the susceptibility of IL-17-deficient mice to Con A-induced hepatitis.…”

Section: Exogenous Il-22 Injection Protects Il-23p19-deficient Mice Fmentioning

confidence: 99%

“…The proinflammatory/pathological nature is apparent in mouse models with diseases such as psoriasis [4] and rheumatoid arthritis [22], and T. gondii infection [11]. In contrast, IL-22 plays protective roles and has tissue-protective and antimicrobial properties in several mouse models with diseases such as inflammatory bowel disease (IBD) [23], hepatitis [24] and infection with invading pathogenic bacteria [10,25,26].…”

Section: Introductionmentioning

confidence: 99%

“…However, since the hepatoprotective effect of IL-22 appears to be more constant than that of IL-23, this may suggest that IL-23 induces the production of other proinflammatory cytokines as well. Taken together, these results suggest that although endogenous IL-23-mediated IL-22 production is involved in hepatoprotection, exogenous IL-23-mediated IL-17 production may contribute to hepatopathology.IL-17-deficient mice show ameliorated hepatitis and exogenous IL-23 fails to protect them from hepatitisTo the best of our knowledge, there are two conflicting reports as to the susceptibility of IL-17-deficient mice to Con A-induced hepatitis [24,31]. Therefore, to further clarify the role of IL-17 in Con A-induced hepatitis, we investigated the susceptibility of IL-17-deficient mice to Con A-induced hepatitis.…”

mentioning

confidence: 99%

“…IL-6 has the ability to induce IL-22 production [4], and IL-6-deficient mice were shown to be highly susceptible to liver damage [30]. However, IL-6-deficient mice were reported to have no impairment in IL-22 expression during Con A-induced hepatitis [24]. IL-23 also has the ability to induce the production of .…”

mentioning

confidence: 99%

“…IL-23 also has the ability to induce the production of . In addition, there are conflicting reports as to the role of IL-17 in Con A-induced hepatitis and the susceptibility of IL-17-deficient mice to hepatitis [24,31]. Therefore, whether or not IL-23 plays any role in the regulation of hepatitis remains unknown.…”

mentioning

confidence: 99%

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

Morishima

Mizoguchi

et al. 2011

Eur J Immunol

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IL-23 plays a critical role in the expansion of highly proinflammatory Th17 cells secreting . 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-c and TNF-a. 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.Key words: Hepatitis . IL-17 . IL-22 . IL-23Supporting Information available online Introduction IL-23 is a heterodimeric cytokine which belongs to the IL-6/IL-12 family and plays a key role in autoimmune and inflammatory disorders [1]. IL-23 acts on memory-type cells [2] and induces the production of . Moreover, IL-23 is an essential factor in the survival and expansion of Th17 cells [5], which produce cytokines including IL-17, IL-17F, . p19-deficient mice are highly resistant to the development of experimental allergic encephalomyelitis (EAE) [7], and it has been shown that the IL-23-dependent production of IL-17, but not , is important for the pathogenesis of autoimmune 2828diseases such as EAE [9]. Recent studies have also revealed that the IL-23-dependent production of IL-22, but not IL-17, plays a critical role in protection against subsequent infection. In infection with an attenuated strain of Salmonella enterica serovar Enteritidis, p19-deficient mice showed reduced survival and exacerbated liver necrosis only in the absence of IL-12 in an IL-17-independent manner [10]. In peroral infection with Toxoplasma gondii, which leads to the development of small intestine inflammation, the IL-23-dependent upregulation of IL-22 is essential for the development of ileitis; on the other hand, IL-17 is downregulated and dispensable [11].IL-22 is a member of the IL-10 cytokine family and plays important roles in inflammation, immune surveillance and tissue homeostasis [12][13][14][15] [10,25,26].Recently, we demonstrated that Notch, which is an evolutionally conserved molecule that controls cell fate decision in a variety of cells [27,28], drives IL-22 secretion by stimu...

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Section: Exogenous Il-22 Injection Protects Il-23p19-deficient Mice Fmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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

Morishima

Mizoguchi

et al. 2011

Eur J Immunol

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Th17 Cells

Noack

Miossec

2017

Inflammation - From Molecular and Cellular Mechanisms to the Clinic

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Optimization of the properties of chitosan lactate/hyaluronan film

Kukolíková

Bakoš

Alexy

et al. 2006

J of Applied Polymer Sci

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Polyelectrolyte complexes represent attractive class of polymer-based materials, finding an irreplaceable role in biomaterial preparation for tissue engineering or drug delivery beads. Mechanical properties, physical properties, and enzymatic degradation of the film prepared from chitosan lactate/hyaluronan polyelectrolyte complex, crosslinked with starch dialdehyde derivatives, were studied to optimize its composition. This work represents an example demonstrating how a minor modification of the modified complex composition changes final properties of the prepared film and emphasizes enormous variations in complex formation by crosslinking. To obtain sufficiently useful information, experimental design was employed.

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Interleukin-22 but Not Interleukin-17 Provides Protection to Hepatocytes during Acute Liver Inflammation

Cited by 565 publications

References 55 publications

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

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

Th17 Cells

Optimization of the properties of chitosan lactate/hyaluronan film

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