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Negative Regulation of Type I Interferon Induction in Dendritic Cells

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2011, Doctor of Philosophy, Case Western Reserve University, Pathology.
Type I interferon (IFN) regulates innate and adaptive immunity. It protects host cells against viral infection. Many microorganisms have evolved successful mechanisms to inhibit host type I IFN response. Excessive type I IFN is associated with autoimmune diseases such as systemic lupus erythematosus (SLE). Studying the negative regulation of type I IFN will help understand the pathogenesis of infectious diseases and potential therapeutic control of type I IFN in SLE. In murine bone marrow derived dendritic cells (DCs), we found two mechanisms that can inhibit type I IFN production in DCs. First, CpG-B ODNs, previously known as weak IFN inducers, globally inhibit type I IFN production by multiple Toll-like receptor (TLR)-dependent and –independent pathways. It involves transcriptional regulation of first-wave type I IFN induction downstream of multiple receptors by inhibiting binding of IRF1 and chromatin remodeling at the IFN-β and IFN-α4 promoters. Second, M. tuberculosis and TLR2 agonists specifically inhibit MyD88-dependent (TLR7/TLR9-induced) type I IFN induction. The inhibition is mediated through a new protein synthesis –independent direct intracellular mechanism that is correlated with rapid depletion of IRAK1. Overall, further investigation of these mechanisms may help us understand the role of type I IFN in infections and vaccines when multiple TLR agonists are present and may provide therapeutic targets for controlling type I IFN production in vivo.
Thomas Hamilton (Committee Chair)
Clifford Harding (Advisor)
George Dubyak (Committee Member)
Henry Boom (Committee Member)
Derek Abbott (Committee Member)
Clive Hamlin (Committee Member)
122 p.

Recommended Citations

Citations

  • Liu, Y. (2011). Negative Regulation of Type I Interferon Induction in Dendritic Cells [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1310149509

    APA Style (7th edition)

  • Liu, Yi. Negative Regulation of Type I Interferon Induction in Dendritic Cells. 2011. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1310149509.

    MLA Style (8th edition)

  • Liu, Yi. "Negative Regulation of Type I Interferon Induction in Dendritic Cells." Doctoral dissertation, Case Western Reserve University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1310149509

    Chicago Manual of Style (17th edition)