Panel B shows another chronic HCV patient who had only a few scat

Panel B shows another chronic HCV patient who had only a few scattered FGL2-positive cells (brown cells) in the explanted liver

and has not required any treatment for recurrent HCV infection. Figure 6. Increased expression of FGL2 in the explanted liver correlates with severity and recurrence of HCV infection. A: Chronic HCV patient with many FGL2-positive cells (brown cells) in the explant, who developed aggressive recurrent disease that did not respond … FGL2: MECHANISM OF ACTION Based upon the data collected to date, it has been shown that FGL2 is integral to both the innate and the adaptive Inhibitors,research,lifescience,medical immune responses. This is not surprising as FGL2 is a molecule that has been conserved through evolution from single-cell organisms such as the ameba to selleck kinase inhibitor higher primates. We propose a mechanistic model by which FGL2 exerts its immunoregulatory effects (Figure 7). Treg cells secrete FGL2, which then binds to the inhibitory FcγRIIB receptor expressed on DC. Binding of FGL2 to FcγRIIB down-regulates immune activation of DC as selleck indicated by inhibition of expression Inhibitors,research,lifescience,medical of the maturation markers CD80, CD86, and MHCII. This suppressive effect of FGL2 on DC was Inhibitors,research,lifescience,medical shown to be mediated through inhibition of NF-κB nuclear translocation.47 DC that are exposed to FGL2 would

be therefore less effective in inducing proliferation and effector function of helper and cytotoxic Inhibitors,research,lifescience,medical T lymphocytes. Suppression of helper T cell activation and DC maturation by FGL2 could lead indirectly to inhibition of T-dependent and T-independent B cell responses, respectively. As demonstrated

by our in vitro studies, FGL2 can also directly induce apoptosis in B cells upon binding to the inhibitory FcγRIIB receptor, which is known to be expressed on B cells. The indirect and direct suppressive activities of FGL2 result in inhibition of the immune response against the HCV, leading to viral persistence and chronic infection. Figure 7. A proposed Inhibitors,research,lifescience,medical model of FGL2 immunoregulatory activities. Treg production of FGL2 down-regulates adaptive immune responses through binding to the inhibitory Entinostat FcγRIIB receptor, which is expressed on antigen-presenting cells. The suppressive activities … CONCLUSIONS AND FUTURE DIRECTIONS HCV infection is a major world health problem and the leading cause of HCC worldwide. Disturbances in Treg cell function or number have now been shown to contribute to failure of clearance of HCV and the development of chronic hepatitis. FGL2 has been shown to be an important effector molecule of Treg cells and was demonstrated to play a key role in the pathogenesis of both experimental and human viral hepatitis. Measurement of levels of sFGL2 in plasma of patients appears to predict both the course of HCV disease and response to anti-viral therapy, and, as such, FGL2 as a biomarker may become an important diagnostic reagent in the management of HCV patients.

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