Sophie Janssens Lab

Research focus

Our research team focuses on the role of the unfolded protein response (UPR) in immune cells. The UPR is an adaptive response that is typically initiated upon accumulation of improperly folded proteins in the endoplasmic reticulum (ER). It monitors the health status of the ER through a triad of sensors, IRE1, PERK and ATF6. These proteins reside in the ER membrane and activate both transcriptional and translational machinery to restore homeostasis during ER stress. The importance of this stress response in immunity is underscored by the identification of gene signatures of UPR activation in both human disease and vaccine responses. Moreover, several UPR proteins have adopted new functions in immune cells, acting both as sensors of danger and regulators of immune responses.

Recent work from the Janssens group and others has shown that the UPR is selectively activated as part of a developmental program in immune cells, independent of accumulation of unfolded proteins. In cDC1 (formerly called CD8α) conventional dendritic cells, the UPR sensor IRE1α and its downstream transcription factor XBP1s are constitutively active and deficiency of XBP1s leads to defects in crosspresentation of dead cell-derived antigens. This is caused by activation of an IRE1 dependent process called Regulated IRE1 dependent RNA decay (RIDD) in XBP1 deficient type 1 cDCs and the subsequent degradation of messenger RNAs coding for cross-presenting machinery. The loss of RIDD on top of XBP1 deficiency restored cross-presentation capacity in DCs, leaving the role of the IRE1/XBP1 branch in cDC1s enigmatic.

An unbiased analysis of the transciptome of wild type, XBP1 deficient and XBP1/IRE1 deficient cDC1s revealed a novel physiological function for IRE1 in cDC1s, which was highly DC specific. Future research of my lab will examine this novel role of IRE1, both in steady state conditions and during infection.
To approach this question, we follow activation of IRE1 and/or RIDD at single cell level in different tissues in vivo, making use of highly specific reporter systems. We combine advanced immunology with cell biology and signal transduction approaches. This gives us the unique opportunity to couple IRE1 function, activation, oligomerisation and/or subcellular localisation to distinct DC functions in presence or absence of an infection.

IRE1KO_dentritic-cell.jpg​​

WT_dentritic-cell.jpg

TEM pictures showing ER morphology in WT (up) and IRE1-1 KO (down) CDC1 dentritic cells.

Publications

The Unfolded Protein Response in the Immune Cell Development: Putting the Caretaker in the Driving SeatTavernier S, Lambrecht B, Janssens SCURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY, 414, 45-72, 2018
Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survivalTavernier S Osorio F Vandersarren L Vetters J Vanlangenakker N Van Isterdael G Vergote K De Rycke R Parthoens E Van De Laar L Iwawaki T Del Valle J Hu C Lambrecht B* Janssens S*NATURE CELL BIOLOGY, 19, 698-710, 2017* These authors contributed equally
The unfolded-protein-response sensor IRE-1alpha regulates the function of CD8alpha+ dendritic cellsOsorio F Tavernier S Hoffmann E Saeys Y Martens L Vetters J Delrue I De Rycke R Parthoens E Pouliot P Iwawaki T Janssens S* Lambrecht B*NATURE IMMUNOLOGY, 15, 248-57, 2014* These authors contributed equally
Emerging functions of the unfolded protein response in immunityJanssens S, Pulendran B, Lambrecht BNATURE IMMUNOLOGY, 15, 910-919, 2014
PIDD mediates NF-kappaB activation in response to DNA damageJanssens S, Tinel A, Lippens S, Tschopp JCELL, 123, 1079-92, 2005

Job openings

News

ERC Consolidator Grant for Sophie Janssens

10/12/2018 - The European Research Council (ERC) has awarded Sophie Janssens, group leader at the VIB-UGent Center for Inflammation Research, a consolidator grant. These grants are rewarded to scientists who already showed that they are able to run their own lab

Sophie Janssens

Sophie Janssens

Research area(s)

Model organism(s)

Bio

​PhD: Ghent  Univ., Ghent, Belgium, '98-'03
Postdoc: Univ. Lausanne, Lausanne, Switzerland, '03-'05
Postdoc: Ghent Univ., Ghent, Belgium, '05-'07
Postdoc: Univ. of Antwerp, Antwerp, Belgium, '07-'11
Full Professor: Ghent Univ., Ghent, Belgium since 2011
Group leader VIB as of March 2018​

Contact Info

VIB-UGent Center for Inflammation ResearchUGent-VIB Research Building FSVMTechnologiepark 927 9052 GENTRoute description