Mike Dolan

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.

Spatiotemporal Analysis of Remyelination Reveals a Concerted Interferon-Responsive Glial State That Coordinates Immune Infiltration Remyelination, the process by which axons are re-encased in myelin after injury, is a critical step in restoring brain function, yet the dynamics from initial injury to repair remain poorly characteri...

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!

Our lab website is live: dolanlab-tcd.com