New findings on immune cells in the brain - Charité researchers identify protein CLIC1 as a key switch in microglia - the immune cells of the brain
What was the research question or scientific inquiry behind your study?
Microglia are the brain’s resident immune cells and act as its first line of defence. A striking feature of these cells is their ability to use their fine, highly motile processes to continuously scan and monitor the surrounding brain tissue. In doing so, they detect disturbances at an early stage, clear away cellular debris or potential pathogens, and help maintain balance in the brain. How exactly this motility and the cells’ immune responses to harmful influences are controlled remains incompletely understood and was the central focus of our study.
How did you approach the topic?
We systematically analysed microglial movement in mouse brain tissue using multiphoton microscopy. In addition, we worked with a mouse model carrying transplanted human microglia as well as with human brain tissue that had been removed during neurosurgical procedures and donated for research with consent. Through pharmacological and genomic approaches, we identified the protein Chloride Intracellular Channel 1 (CLIC1), and generated a mouse line lacking this protein to study its role in microglial motility and immune function.
What did you discover?
We found that CLIC1 regulates the motility and ramification of microglial processes and is therefore a central factor in the continuous surveillance and protection of brain tissue. Mechanistically, our data indicate that CLIC1 acts as a scaffold protein that stabilizes these processes. In addition, CLIC1 controls the release of the strongly proinflammatory molecule interleukin 1β from activated microglia. Importantly, we found that these CLIC1-dependent functions are fully conserved in microglia in the human brain.
Was there anything that surprised you?
Contrary to its name (Chloride Intracellular Channel 1), in microglia CLIC1 does not act as an ion channel that transports chloride across the cell membrane. Instead, it carries out its tasks as a structural protein and as an enzyme.
What’s your takeaway?
CLIC1 plays an important role in both the healthy and diseased brain. Microglia are involved in nearly all neurological disorders and can significantly influence how these diseases progress, particularly through inflammatory processes. Our discovery that CLIC1 controls the release of proinflammatory interleukin 1β and that it is found almost exclusively in microglia in the human brain highlights its therapeutic potential to contain inflammation in the brain.
Source
Rifat & Bickel et al. The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation. Science Advances 2025 October 22. DOI: 10.1126/sciadv.ads9181
Contact
Prof. Christian Madry
Institute of Neurophysiology
Charité – Universitätsmedizin Berlin
Links
Citation: Charité
