Project

The role of the IRE1/XBP-1 axis in dendritic cells in antiviral immunity

Duration
01 January 2015 → 31 December 2020
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other basic sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other clinical sciences
    • Other health sciences
    • Nursing
    • Other paramedical sciences
    • Laboratory medicine
    • Palliative care and end-of-life care
    • Regenerative medicine
    • Other translational sciences
    • Other medical and health sciences
Keywords
antiviral immunity IRE-1/XBP-1
 
Project description

The role of the unfolded protein response (UPR) in immune cell functioning is incompletely understood. We recently found that the IRE-1/XBP-1 axis - one of the main branches of the UPR – is constitutively active and required for the function of one specific subset of dendritic cells (DCs) that is specialized in antigen crosspresentation during viral infections. IRE-1 has both endonuclease and kinase activity. Its main substrate is the transcription factor XBP-1, but in addition IRE-1 also degrades several mRNAs in a process called Regulated IRE-1 Dependent Decay (RIDD). So far, most substrates for RIDD have been uncovered by using genetic loss of function models for XBP-1, which triggers hyperactivation of IRE-1 and concomitant RIDD. The true physiological role of RIDD remains as yet highly speculative. In the current project, we would like to explore the role of RIDD and the IRE-1/XBP-1 axis in DCs during viral infection. More specifically, we want to investigate the hypothesis that IRE-1-mediated RIDD activation could function as a potential mechanism to time and regulate MHC-I dependent crosspresentation, as well as control the anti-viral state in DCs.