Akkermansia muciniphila-derived myelin mimetics activate myelin-specific T cells and exacerbate experimental autoimmune encephalomyelitis 2883

Description Numerous clinical studies have identified an increased abundance of the commensal gut bacterium Akkermansia muciniphila (AKK) in individuals with multiple sclerosis (MS). Additionally, microbial transplants from MS patients were associated with the exacerbation of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, our understanding of how commensal bacteria may promote autoimmunity remains limited. In this study, we demonstrate that AKK colonization exacerbates EAE development and AKK can be processed by dendritic cells to activate myelin oligodendrocyte glycoprotein (MOG)35-55-specific T cells. Our recent findings indicate that the gut microbiome may produce myelin antigen-mimicking peptides, potentially serving as triggers for central nervous system autoimmunity. Thus, we hypothesized that AKK-derived peptides can activate MOG35-55-specific T cells. Notably, we identified several epitopes within AKK that mimic MOG35-55. We synthesized the peptide from AKK displaying the highest homology with the MHC II-peptide-T cell receptor binding area of MOG35-55. This peptide stimulated cytokine production by MOG35-55-specific CD4+ T cells, indicating its capacity to function as a molecular mimic of MOG35-55. In conclusion, our findings suggest that AKK-derived peptides can activate MOG35-55-specific T cells and thus exacerbate EAE. Our results may help reveal potential therapeutic targets for MS. Funding Sources Supported by the National Natural Science Foundation of China (82371350).