Session 1: Animal Models of MS and the Role of T Cells

Location: VND 2291A

8:30 - 9:15 am: 
Animal models of MS and the role of T cells (1h15) 
Moderator: Dr. Manu Rangachari 

8:30 - 9:15 am
Animal models of MS and introduction to T cells - Dr. Manu Rangachari (45 mins)
Animal models of CNS autoimmunity and demyelination will be described, with a particular focus on the experimental autoimmune encephalomyelitis (EAE) model of MS.

9:15 - 9:45 am:
Making progress: Modeling progression using an Nr1h3 variant identified in families with primary progressive MS  - Dr. Jacqueline Quandt
Developing effective treatments for the progressive phase of MS is a major challenge because of our limited understanding of the biological processes driving progression, and the lack of preclinical models presenting the spectrum of progressive MS characteristics. To address this challenge, we have created constitutive and inducible knock-in mice harboring a nuclear receptor subfamily 1 group H member 3 (Nr1h3) missense mutation (R413Q) homologous to the NR1H3 mutation (R415Q) identified in 7 patients diagnosed with MS from two families. These patients present a highly debilitating and rapidly progressive clinical course, linking biological disruption of the NR1H3 pathways to the development of PPMS. The NR1 family of proteins are key regulators of macrophage function, controlling transcriptional programs involved in lipid/cholesterol homeostasis and inflammation. Given the role of NR1H3 and its targets in lipid transport and immune modulation, we aimed to define mechanisms driving MS risk, severity, and progression. The Nr1h3 model shows subtle myelin dysregulation, a more pathogenic T cell and myeloid phenotype, increased disability, neurodegeneration, and reduced ability to repair, elucidating key mechanisms underlying aggressive and progressive MS.    
Objectives: 
 •To review evolving concepts and processes relevant to the pathophysiology of aggressive/ progressive MS  
•To present a novel preclinical model with translational relevance to progression in MS