Summary: A recent publication from Dr. Jennifer Gommerman’s research team offered new insights into the molecular processes that lead to compartmentalized inflammation in the brain – a key driver of disability progression in MS. Using mice with MS-like disease, they showed that formation of immune cell clusters within protective membranes of the brain contribute to compartmentalized inflammation, and that these clusters can be effectively targeted by Bruton’s Tyrosine Kinase inhibitor (BTKi). The researchers also presented a new way to identify people who may be experiencing this type of inflammation and are more likely to benefit from targeted treatments with medications like BTKi. This finding could lead to a more personalized and effective approach to treating MS progression.
Background: Compartmentalized inflammation occurs when immune cells become trapped within the central nervous system causing injury to the underlying brain tissue (e.g., grey matter injury). In MS, immune cells can form clusters near areas of nerve fibre damage – known as ‘Tertiary Lymphoid Tissues or TLT – which are strongly linked to disability progression. As TLT form within protective membranes surrounding the brain, they are difficult to treat with current MS therapies. A newer class of drugs, called BTKi, can reach the brain and could potentially be used to target these immune clusters.
Results: Dr. Jennifer Gommerman’s research team at the University of Toronto developed a mouse model of MS (experimental autoimmune encephalomyelitis, or EAE) that closely mimics TLT formation in the brain. They found that treating these mice with the BTKi, remibrutinib, reduced TLT formation and grey matter injury in the brain. The treatment worked by disrupting two key molecular pathways (BTK and Lymphotoxin pathways).
The team also reported that the presence of TLT and grey matter injury corresponded to measurable changes in two proteins (CXCL13:BAFF) in the brain of EAE mice and cerebrospinal fluid of people with MS. A high CXCL13:BAFF ratio was associated with TLT formation and grey matter injury, while BTKi treatment led to decreased CXCL13:BAFF levels.
Impact: These findings deepen our understanding of how compartmentalized inflammation develops in the brain and how it may be targeted by treatments such as BTKi. Importantly, this study introduces a new way of identifying people with MS who may be experiencing compartmentalized inflammation (by measuring CXCL13:BAFF levels) and would benefit most from personalized, targeted treatments. While these results are promising, further validation is still needed through additional studies.
*This research is funded in partnership with the National MS Society (US).
References:
- Article published in Nature Immunology on January 2, 2026 – Lymphotoxin-dependent elevated meningeal 1 CXCL13: BAFF ratios drive grey matter injury.
Learn more about Dr. Gommerman’s research: