IMMUNOLOGY2026™ Conference Recordings For Attendees-Complement as Driver of Age-dependent Progression: Insights from Multiple Sclerosis and a Mouse Model

Video Transcription

Video Summary

The transcript features two talks on local complement biology.<br /><br />Valeria Ramaglia discussed progressive multiple sclerosis (MS), emphasizing that it differs fundamentally from relapsing-remitting MS and currently lacks effective treatments. She proposed that inflammation in the leptomeninges produces harmful molecules that accumulate in cerebrospinal fluid and damage the brain inward, with the hippocampus especially vulnerable. Using an age-dependent mouse model of experimental autoimmune encephalomyelitis, her lab reproduced progressive-like, non-remitting disease in aged mice, along with persistent meningeal inflammation, hippocampal demyelination, synapse loss, and brain atrophy. Proteomic and single-cell analyses identified complement, especially C3, as enriched in aged disease. C3 was produced in the meninges, deposited in the hippocampus, and blocking C3 activation with a viral inhibitor partially rescued disability in aged mice. Human MS tissue also showed a link between meningeal inflammation, hippocampal damage, and C3 deposition on oligodendrocyte lineage cells.<br /><br />The second speaker, Dr. Wu, described how the gut microbiota shape local complement, especially C3, in mucosal tissues. She showed that fecal C3 is microbiota-dependent, varies by mouse vendor and in healthy humans, and can be transferred by microbiota transplantation. Gut luminal C3 helped protect against Citrobacter infection, mainly via the alternative pathway, with stromal cells as a major C3 source. She also presented emerging work showing that microbiota associated with recurrent UTI can induce C3 in the bladder, suggesting distant mucosal immune regulation.

Meta Tag

Date April 18, 2026 9:45 AM - 11:15 AM

Room 104C

Session Complement - Key Modulator of Tissue Autoimmunity and Inflammation, Sponsored by the Intl. Complement Soc. (ICS)

Speaker Valeria Ramaglia

Track Basic Autoimmunity (BA)

Year 2026

Keywords

progressive multiple sclerosis

complement C3

meningeal inflammation

hippocampal demyelination

experimental autoimmune encephalomyelitis

gut microbiota

mucosal immunity

bladder infection

April 18, 2026 9:45 AM - 11:15 AM

104C

Complement - Key Modulator of Tissue Autoimmunity and Inflammation, Sponsored by the Intl. Complement Soc. (ICS)

Valeria Ramaglia

Basic Autoimmunity (BA)

2026