Basic—Liver, Pancreas, and Biliary TractMyeloid STAT3 Inhibits T Cell-Mediated Hepatitis by Regulating T Helper 1 Cytokine and Interleukin-17 Production
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Animals
Eight- to 10-week-old male mice were used in all studies performed. T cell-specific STAT3 knockout (STAT3T-cell−/−), myeloid-specific STAT3 knockout (STAT3Mye−/−), STAT3Mye−/−STAT1−/−, and STAT3Mye−/−IL-17−/− mice are described in the Supplementary Materials and Methods. For each group, respective littermates were used as wild-type mice. IL-17A−/− mice on a C57BL/6 background were provided generously by Dr. Iwakura of the University of Tokyo. IL-6−/−, IL-10−/−, and IFN-γ−/− mice on a C57BL/6
Activation of STAT3 in Myeloid Cells and T Cells During Con A-Induced Hepatitis
Our previous studies showed that STAT3 and STAT1 were activated in the liver during Con A-induced hepatitis.15 Here, we showed by immunostaining that STAT3 activation occurs not only in hepatocytes but also in virtually all other nonparenchymal cells including inflammatory cells (Figure 1A). Next, we found that STAT3 and STAT1 were also activated in the spleen after Con A injection (Figure 1B). Flow cytometry analyses further revealed that STAT3 and STAT1 phosphorylation occurred in CD3+ T
Discussion
T-cell activation in antigen dependent- (eg, hepatitis C virus [HCV] and hepatitis B virus [HBV]) as well as in antigen-independent- (eg drug intoxication, alcoholic liver diseases) mediated hepatitis has been shown to play a critical role in the pathogenesis of liver diseases.1, 2, 3, 4, 5, 6, 7 For example, in chronic HCV infection, whereas the virus itself has a noncytolytic function, activation of CD8+ T cells kills viral infected hepatocytes via releasing perforin and granzyme, while
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the intramural program of NIAAA, NIH.