CXCR3+ T cells in multiple sclerosis correlate with reduced diversity of the gut microbiome

Abstract

Multiple sclerosis (MS) is a genetically mediated autoimmune disease characterized by inflammation in the central nervous system (CNS). Disease onset is thought to occur when autoreactive T cells orchestrate a cascade of events in the CNS resulting in white and grey matter inflammation and axonal degeneration. It is unclear what triggers the activation of CNS-reactive T cells and their polarization into inflammatory subsets. Mounting evidence from animal and human studies supports the hypothesis that the gut microbiome affects MS pathogenesis. We investigated the association between the gut microbiome and inflammatory T cell subsets in relapsing-remitting MS patients and healthy controls. Gut microbiome composition was characterized by sequencing the V4 region of the 16S rRNA gene from fecal DNA, and inflammatory T cell subsets were characterized by flow cytometry. We identified an altered gut microbiome in MS patients, including decreased abundance of Coprococcus, Clostridium, and an unidentified Ruminococcaceae genus. Among circulating immune cells, patients had increased expression of CXCR3 in both CD4 and CD8 T cells, and both CD4+CXCR3+ and CD8+CXCR3+ populations expressing the gut-homing α4β7 integrin receptor were increased. Finally, we show that alpha diversity inversely correlated with a CXCR3+ Th1 phenotype in MS. These findings indicate the presence of an aberrant gut-immune axis in patients with MS.

Keywords

• Microbiome
• Multiple sclerosis
• Autoimmunity
• CXCR3
• Th1