Th198 - Can the Gut Microbiota Trigger Autoimmune Responses Through Molecular Mimicry in Multiple Sclerosis? An in Vitro Study

Abstract Text: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by demyelinating inflammatory lesions of the central nervous system (CNS). Mounting evidence suggests that the gut microbiota can trigger autoimmune responses, which may potentially contribute to MS onset through molecular mimicry mechanisms. In this in vitro study we investigated whether sterilized culture supernatants or cell pellets of bacteria isolated from MS patients activated 2d2 TCR-MOG reactive T cells through B cell- and dendritic cell- mediated antigen presentation. Bacterial pellets were used to prime antigen presenting cells and assess their ability to stimulate 2d2 CD4 T cells. Our results indicate that specific bacterial pellets promote Th1/Th17 polarization as evidenced by increased expression of T-bet and RORγt compared to myelin oligodendrocyte glycoprotein (MOG) peptide control stimulation. In addition, certain bacteria increased CD44 expression in T cells, suggesting their activation. Some bacterial pellets also induced IL-17 production, suggesting their potential role in pro-inflammatory responses. B cells exposed to specific bacterial pellets and supernatants showed differential production of IL-23 and IL-10, highlighting the ability of gut microbiota to modulate inflammatory and immunoregulatory in MS. These in vitro findings support the hypothesis that gut microbiota may contribute to MS by promoting the activation of autoreactive T cells through molecular mimicry. Further studies are needed to confirm these results in vivo and elucidate the role of microbiota-immune interactions in triggering MS.