Canadian Society for Immunology 2023 35th Annual Meeting
F
rom June 6-9, immunologists across the country gathered in the charming Eastern township of Orford, Quebec for the 35th annual meeting of the Canadian Society for Immunology (CSI) at the Hôtel Chéribourg. While the rainy weather dissuaded most from exploring the scenic trails around the conference site, the beautiful scenery nonetheless acted as a welcoming backdrop to four days of exciting immunology and networking with our colleagues from coast-to-coast.
KEYNOTE CSI 2023 opened with a keynote address delivered by Dr Luke O’Neill (Trinity College Dublin), showcasing how lessons learned from rare human diseases can help us better understand the underlying immunology for broader therapeutic applications. Thematic to this issue of IMMpress Magazine, the unifying concept of this address was how mitochondrial dysfunction underpins many flavours of inflammatory and autoimmune diseases. Poised at the intersection of biochemistry and immunology, Dr O’Neill spoke on the role of two Krebs’ cycle intermediates, itaconate and fumarate – molecules generated in the mitochondria during the process of metabolic respiration – in both metabolism and modulating the immune response. Macrophages stimulated by lipopolysaccharides (LPS), a major bacterial toxin, upregulate both itaconate and fumarate. Dr O’Neill and his team demonstrated that itaconate and related derivatives inhibit proteins involved in inflammatory pathways such as NLRP3 and JAK1, leading to anti-inflammatory and anti-microbial effects. On the other hand, fumarate accumulation, which occurs through fumarate hydrogenase inhibition, drives type I interferon release via mitochondrial stress and induced inflammatory responses. Interestingly, fumarate dehydrogenase has been found to be repressed in lupus patients, implying a role for metabolic dysregulation in certain autoinflammatory diseases. The stories of these two metabolites emphasized the untapped potential of immunometabolites as both therapeutic targets and agents across a spectrum of immune-mediated diseases.
28 IMMpress Vol. 11 No. 2 2023
PERSONALIZED IMMUNITY The first symposium explored how different biological aspects can be considered to tailor therapies for effective clinical outcomes. Dr Ivona Aksentijevich (National Human Genome Research Institute) discussed how patient stratification by molecular diagnosis is critical in informing targeted therapies, particularly in cases of autoinflammatory diseases. Next, Dr Keke Fairfax (University of Utah) spoke on how helminth infection by Schistosoma mansoni can interact with biological sex to modulate the risk of developing metabolic syndromes, conferring protection against atherosclerosis, obesity, and diabetes in male, but not female, mice. Dr Naoto Hirano (University of Toronto) then brought us to the other end of the spectrum of personalized medicine, introducing the generation of an HLA-agnostic chimeric antigen receptor (CAR) T cell therapy against the tumour antigen WT1 that can bypass the issue of cell therapy-patient HLA class II incompatibility. Dr Channakeshava Umeshappa (Dalhousie University) described a novel peptide-MHCII nanomedicine strategy that induces the differentiation of a novel regulator Maf+LiNKTR1 invariant natural killer T cell population that may represent a potential therapy in autoimmune liver diseases. Concluding the first symposium, Dr Marc Horwitz (University of British Columbia) demonstrated that latent chronic Epstein-Barr virus infection can drive increased susceptibility and severity of multiple sclerosis (MS) in mice, and discussed how this approach can be adapted using human immune cells to create personalized preclinical models of MS for therapeutic testing.
