We report dysregulated type 3 responses in fibrotic lesions with increased IL-17<sup>+</sup>CD4<sup>+</sup>/FOXP3<sup>hi</sup>CD4<sup>+</sup> ratio and increased IL-17 and IL-22 production in advanced liver fibrosis.
In the present study, we evaluated the capacity of the BM-MSCs in the modulation of cytokines milieu and signal transducers, based on unique inflammatory genes Il17a and Il17f and their receptors Il17rc and their effect on the IL6/STAT3 pathway in CCl4-induced liver fibrosis in rats.
In Mdr2<sup>-/-</sup> mice, we found development of liver fibrosis and inflammation to require hepatic activation of γδ TCR<sup>+</sup> cells and production of IL17 mediated by exposure to L gasseri.
When we depleted the Vγ2 T cells in infected mice, the percentage of neutrophils in blood and spleen decreased significantly, the liver fibrosis in the granulomas was reduced, and the level of IL-17A in the serum decreased (<i>P</i> < 0.05).These results suggest that during <i>S. japonicum</i> infection, Vγ2 T cells can recruit neutrophils and aggravate liver fibrosis by secreting IL-17A.
Splenic Th9 and Th17 cells, plasma concentrations and liver expression of IL-9 and IL-17A were significantly elevated in mice with hepatic fibrosis compared with controls.
To test the role of inflammation severity in stem cell-mediated tissue repair, we employed mice with carbon tetrachloride-induced advanced liver fibrosis and found that although MSCs alone were effective, concurrent administration of Dex abrogated the therapeutic effects of MSCs on fibrin deposition, serum levels of bilirubin, albumin, and aminotransferases, as well as T-lymphocyte infiltration, especially IFN-γ(+)CD4(+) and IL-17A(+)CD4(+)T cells.
We examined IL-17 levels in serum and tissues from patients with chronic hepatitis B virus infection (HBV), and especially evaluated the role of IL-17 in the pathogenesis and progression of liver fibrosis.
Using cholestatic and hepatotoxic models of liver injury, we compared the development of liver fibrosis in wild-type mice with that of IL-17RA(-/-) mice and of bone marrow chimeric mice devoid of IL-17 signaling in immune and Kupffer cells (IL-17RA(-/-) to wild-type and IL-17A(-/-) to wild-type mice) or liver resident cells (wild-type to IL-17RA(-/-) mice).