Group van der Vlist
Group van der Vlist
The response of our immune system needs to stay within limits: too little allows pathogens and cancers to grow, too much leads to immune pathogenesis or autoimmunity. Inhibitory immune receptors are in place to limit or prevent immune activation. They do so by placing a threshold for activation, or negative feedback on immune activation. Our lab’s goal is to use inhibitory immune receptors for therapeutic strategies. We aim to inhibit immune responses in (i.e.) autoimmunity, or stimulate immune responses in (i.e.) cancer. However, our data show that the function of inhibitory receptors is not always inhibitory. To be able to safely target inhibitory receptors in the clinic, we need to understand the details of how they work in health and disease.
To reach our goal, we study the overall hypothesis that the function of inhibitory receptors is sensitive to the environment. We have discovered that CD200R inhibits immune responses during health, but can potentiate responses during inflammation. CD200R potentiated immune responses in ~50% of systemic lupus erythematosus patients, particularly in patients with lupus nephritis (Science Signaling; BioRXiv). We have extensively characterized the signaling domain of CD200R (PLOS ONE), identified a previously unrecognized activating CD200R-family member expressed by human neutrophils (JLB), and discovered the unexpected but fundamental role of CD200R in macrophage:neuron communication in the periphery and the resolution of inflammatory pain (BioRXiv).
In addition to our work on CD200R, we expanded our research interest to PD-1 and LAIR-1 signaling in cancer models. We study how immune responses to respiratory syncytial virus are affected by inhibitory receptors. With this approach, we study how inhibitory receptors are influenced by multiple disease conditions.
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Michiel van der Vlist
- Ellen Kaan
- Laura Timmerman
- Klasina Chappin