Delighted to give a talk at the wonderful Cambridge Center for Myelin Repair annual symposium in Cambridge, UK. Truly fantastic conference and an amazing community. Thank you to Thora Karadottir and @mssocietyuk.bsky.social for organising!
None of this work would be possible without the mentorship of @bethstevenslab.bsky.social and Evan Macosko. Or the hard work of two phenomenal RAs: @raphaelrakosi.bsky.social and Eric Garcia!
Thank you to all our collaborators and coauthors!
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Summary:
Remyelination depends on a glial-immune axis, initiated by type I interferon signaling that summons lymphocytes. Surprisingly, these cytotoxic CD8 T-cells enhance remyelination.
Full story ➡️ www.biorxiv.org/content/10.1...
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Critically, depleting the most abundant of these lymphocytes — CD8 T-cells — led to reduced oligodendrocyte maturation, directly linking lymphocyte infiltration to successful remyelination.
This was surprising, we expected CD8 T-cells to exert a negative effect on the brain
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What’s the function of IRG?
We demonstrate that IRG secrete CXCL10, a chemokine that recruits lymphocytes into the repairing white matter.
Without this glial-driven recruitment, lymphocyte
infiltration was impaired.
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Third, we discovered a shared interferon-response program across multiple glial types.
These interferon-responsive glia (IRG) clustered around remyelinating white matter — and their formation was dependent on type I interferon signaling.
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Second, we observed a selective infiltration of immune cells specifically during remyelination:
➡️ CD8 T-cells
➡️ Natural killer (NK) cells
These lymphocytes were specifically enriched during the repair phase, not just during damage.
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First, glial and monocyte-derived macrophage states are highly dynamic.
We found extensive transcriptional remodeling across microglia, astrocytes, and oligodendrocyte lineage cells from demyelination through to repair.
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We used a focal demyelination model to study the entire process of white matter injury and repair at high spatial and molecular resolution.
Our goal: capture the real-time cellular and molecular dynamics driving remyelination.
How does the brain repair myelin after injury?
We mapped the full cellular choreography of white matter repair using snRNA-seq + Slide-seqv2, uncovering a type I interferon-driven glial program that recruits lymphocytes to promote remyelination.
www.biorxiv.org/content/10.1...
Details below 👇
Imaging these astrocytes on the surface of cleared brains was a blast!