Multiple sclerosis (MS) is a chronic, degenerative disease of the central nervous system (CNS) characterized by demyelination and axonal damage driven by an immune-mediated inflammatory process. Recent research has focused on the gut-brain axis and the role of gut microbiota in MS. Th17 cells, which have both pro-inflammatory and anti-inflammatory properties, depending on the cytokine that stimulates them, play a crucial role in regulating tissue inflammation and have been implicated in the development of MS. For example, IL-23 is considered as a pro-inflammatory cytokine (45), on the contrary, some types of TGF-β, are known to attenuate the disease in mice models (42). Multiple studies, using experimental autoimmune encephalomyelitis (EAE) murine models, have demonstrated the involvement of Th17 cells in the inflammation and demyelination processes. These studies highlight the recruitment of other immune cells, cytokines, and inflammatory markers, following Th17 cells activation, within the CNS.
Our study aimed to investigate three main objectives: (i) The gain of pro-inflammatory function by T cells in diseases, such as MS, (ii) the interaction and impact of molecules produced by intestinal microbiome on the phenotype of Th17 cells in vitro, thereby elucidating a potential connection between the gut-brain axis and extra-intestinal autoimmune diseases, and (iii) the measurement of various species of microbiota to understand how the modulation of the microbiome with antibiotics could influence the disease.
Our results revealed that Th17 cells in vitro, treated with microbiota-derived fecal filtrate from control mice, increase the expression of pro-inflammatory markers such as IFNγ, IL-17, and CXCR6. Conversely, homeostatic markers such as SLAMF6 were significantly decreased in this group. Moreover, antibiotic treatment played a significant role in reducing specific bacterial species, attenuating the severity of the disease. These findings may enhance our understanding of the underlying pathophysiology of inflammation in multiple sclerosis.