Principal Investigator
Sophie Janssens
Research interests
My lab aims to understand how dendritic cells control the balance between immunity and tolerance. To this end we make use of in vivo mouse models in which we address cell biological questions in dendritic cells mostly in the spleen, but also in other organs in the context of health and disease.
We have 4 main research lines
- The role of IRE1 in dendritic cells, an endonuclease of the unfolded protein response that is highly active in one of the two main conventional DC subsets, cDC1s, but in absence of canonical ER stress triggers. On the contrary, we found that activation of IRE1 in cDC1s is caused by their continuous engulfment of apoptotic cells and concomitant cholesterol influx
- As a follow-up, we study how cholesterol influx and engulfment drive the homeostatic DC maturation pathway in cDC1s
- We are exploring the function of homeostatic mature cDC1s and understand how they contribute to the induction/maintenance of peripheral tolerance
- Finally, we are using infection models to address how DCs maintain tolerance to self in the context of a systemic infection. This final question relates to how DCs determine which antigen becomes presented when both self and pathogen derived antigens are being engulfed simultaneously.
Selected publications
- Bosteels V, Maréchal S, De Nolf C, Rennen S, Maelfait J, Tavernier SJ, Amstelveen S, Vetters J, Van De Velde E, Fayazpour F, Deswarte K, Van Duyse J, Martens L, Bosteels C, Roelandt R, Emmaneel A, van Gassen S, Boon L, Van Isterdael G, Guillas Baudouin I, Altuzar J, Vandamme N, Hoglinger D, De Geest BG, Le Goff W, Saeys Y, Kodi Ravichandran K, Lambrecht BN and Janssens S (2023). LXR signaling controls homeostatic dendritic cell maturation. Sci Immunol. 8(83): eadd3955. PMID: 37172103 doi: 10.1126/sciimmunol.add3955
In this paper we mapped pathways of homeostatic DC maturation and found that apoptotic cell engulfment and cholesterol influx is sufficient to drive the homeostatic cDC1 maturation program. The study was conducted as part of my ERC CoG application (DC-RIDDLE).
Comment in: Bird (2023) Cholesterol controls tolerogenic versus immunogenic DCs 23: 413
- Rennen S, Bosteels V, De Nolf C, Webb G, Van Lil K, Maréchal S, Vetters J, Van De Velde E, Fayazpour F, Roelandt R, Vandamme N, Verstaen K, De Smedt S, Breckpot K, De Geest G, Verbeke R, Lentacker I and Janssens S. Lipid nanoparticles as a tool to dissect dendritic cell maturation pathways. Cell Reports 44(8): 116150 . PMID: 40828654 DOI: 10.1016/j.celrep.2025.116150
In this paper, we propose a flow cytometry-based method and a transcriptional profiling strategy to deconvolute homeostatic from immunogenic mature DCs. In addition, we demonstrate that the cargo and not the lipid nanoparticle itself determines its adjuvanticity, a finding that has broad implications for LNP-based vaccination strategies. The paper is accompanied by a STAR Protocols from van Lil K et al, 2026.
- Janssens S, Rennen S, Agostinis P (2024). Decoding immunogenic cell death from a dendritic cell perspective. Immunol Rev 321(1): 350-370. PMID: 38093416 doi: 1111/imr.13301
This paper, which I wrote together with Patrizia Agostinis from KULeuven, was a follow-up on an EOS program grant (DECODE) in which we were both partners. We here summarize what we do and don’t know of how danger signals are being interpreted by DCs, specifically in conventional DCs in vivo.
- Osorio F, Tavernier S, Hoffmann E, Saeys Y, Martens L, Vetters J, Delrue I, De Rycke R, Parthoens E, Poulliot P, Iwawaki T, Janssens S* and Lambrecht B* (2014) The unfolded-protein-response sensor IRE1a regulates the function of CD8a+ dendritic cells. Nature Immunology 15(3): 248-257 *shared last authorship. PMID: 24441789 doi: 10.1038/ni.2808
Paper dating from the start of my own independent lab in which we explored how IRE1 contributes to dendritic cell functioning.
Comment in: Subramanian M and Tabas I (2014) A new RIDDle in DC-mediated cross-presentation. Nat Imm 15: 213-215
Comment in: Leavy (2014) Signalling: new roles for cell stress sensors. Nat Rev Imm 14: 135
- Janssens S*, Tinel A*, Lippens S and Tschopp J (2005) PIDD mediates NF-kB activation in response to DNA damage. Cell 123(6): 1079-1092 * contributed equally to this paper. PMID: 16360037 DOI: 10.1016/j.cell.2005.09.036
Paper dating from my postdoc in Jurg Tschopp’s lab where I contributed in understanding how one and the same molecule PIDD can induce survival and cell death pathways.
Comment in: Wu ZH, Mabb A, Miyamoto S (2005) PIDD: a switch hitter. Cell 123: 980-982.
