Iris van der Vliet

My research focuses on immune checkpoints — ligand-receptor pairs that switch immune activity on or off, and play a key role in maintaining a healthy brain. In the brain, this balance is largely maintained through the interaction between neurons and microglia, the brain's resident immune cells.

Microglia continuously monitor neurons and help maintain a healthy nervous system, yet how their activity is kept in check at the molecular level is still poorly understood. Neurons display surface signals — such as CD47, CD200, and ligands for the receptor GPR56 — that engage inhibitory receptors on microglia and dampen their activity. When this signaling fails, microglia can become abnormally active.

Previous work from our group showed that these checkpoint molecules behave in opposite ways in multiple sclerosis (MS), where microglia overactivation contributes to lesion formation, and major depressive disorder (MDD), where excessive microglial inhibition may lead to unwanted loss of synapses. Interestingly, depression is highly prevalent among people with MS, and my research aims to unravel whether shared checkpoint dysregulation underlies this connection.

To investigate this, I use post-mortem human brain tissue from MS and MDD patients to examine how these checkpoint receptors are regulated on microglia, combining this with synapse density analysis to assess how microglial activity shapes neuronal connectivity. Ultimately, I aim to understand how the balance between neurons and microglia breaks down in disease, and how this shared mechanism may explain why these two conditions so often occur together.

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