Project #7930
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#7930 : Gene expression profiling in Kupffer cells
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Name of Applicant : Yu Wei
Date of application : 21-02-2017
Unit : Hepacivirus and Innate Immunity
Location : 22-3-312
Phone : 0145688866
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Project context and summary :

The liver is the biggest internal organ that is responsible for metabolism, detoxification and the defense between the host and the external environment. Thus the liver is also an immune organ, which constantly confronts conflicting demands of immunity against pathogens and tolerance to antigens metabolized locally and bacteria products derived from the gut. In homeostasis, many mechanisms ensure suppression of immune response in the liver, which include low expression levels of MHC molecules in liver antigen presenting cells (APC), increased expression of inhibitory molecules and sustained expression of suppressive cytokines such as IL-10 and TGF-b. Thus, several pathogens including hepatitis B virus (HBV) shrewdly exploit the tolerant immune environment in the liver to establish chronic infection. However, inflammation can elicit efficient immune response. To investigate immune response to HBV in the context of inflammation, we used Mdr2-/- mice, which develop cholestatic inflammation in the liver. We show that after injection of HBV to the mice, WT animals develop chronic infection whereas Mdr2-/- mice eliminate the virus. We detected robust viral-specific antibody production in Mdr2-/- mice but not in WT mice. Kupffer cells (KC) are liver-resident macrophages and important APCs, expressing MHC I, MHC II and costimulatory molecules required for T cell activation. The efficient immune response against HBV observed in Mdr2-/- mice prompts us to profile gene expression in Kupffer cells derived from these mice and compare to those from WT mice at the naïve state.

Related team publications :
Tebbi, A. et al. (2016) Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress. Carcinogenesis, 37, 39-48.
Altinel, K. et al. (2016) Single-Nucleotide Resolution Mapping of Hepatitis B Virus Promoters in Infected Human Livers and Hepatocellular Carcinoma. Journal of virology, 90, 10811-10822.
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Project Type : Short
Status : Awaiting Publication

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