By Elodie Vaz | Published on April 10, 2026 | 4 min readMultiple sclerosis
(MS) is a chronic and disabling neurological disease characterized by an
immune-mediated attack on the central nervous system (CNS). This autoimmune
response primarily targets myelin, a protective sheath essential for proper
nerve impulse conduction.
At the root of this
dysregulation is the immune system’s inability to distinguish “self” from
“non-self,” leading to inflammatory reactions against the body’s own
components. While genetic and environmental factors are involved, attention is
increasingly turning to an unexpected player: the gut microbiota.
Alterations in this
microbial ecosystem have been observed in patients with MS, suggesting a role
in modulating immune responses. However, the cellular mechanisms linking the
gut to brain inflammation have remained largely unclear.
Deciphering the
gut–brain axis in MS
A study published on
March 27, 2026, in Science Immunology, led by Professors Shohei Suzuki
and Tomohisa Sujino at Keio University, aimed to elucidate the mechanisms by
which intestinal immune responses contribute to neuroinflammation.
“Growing evidence
shows that the gut microbiota influences neurological diseases […] However, the
mechanisms linking gut microbes, intestinal immunity, and brain inflammation
remain unclear. We sought to identify how intestinal immune responses contribute
to neuroinflammatory diseases,” explained Professor Tomohisa Sujino in a press
release.
A translational
approach from mice to humans
The researchers
relied on the experimental autoimmune encephalomyelitis (EAE) mouse model,
widely used to study MS, and compared these findings with observations in
patients.
Using single-cell
RNA sequencing analyses on intestinal biopsies, they identified an accumulation
of inflammatory Th17 lymphocytes in both mice and MS patients.
In parallel,
co-culture experiments were conducted to assess the ability of intestinal
epithelial cells to present antigens to T lymphocytes. Additionally, transgenic
mice expressing the Kaede protein—with modifiable fluorescence—were used to
track the migration of immune cells from the gut to the CNS.
The gut as a site
of pathogenic T cell activation
The results reveal a
central role for intestinal epithelial cells in activating pathogenic immune
responses. Contrary to their classical function, these cells express major
histocompatibility complex class II (MHC II) molecules and present antigens to
CD4+ T lymphocytes.
This interaction
promotes the differentiation of these lymphocytes into pro-inflammatory Th17
cells, known to be involved in autoimmune diseases. Deletion of MHC II in
intestinal epithelial cells reduced both the generation of these pathogenic
lymphocytes and disease severity in the mouse model.
Tracking experiments
showed that these Th17 lymphocytes, activated in the gut, subsequently migrate
to the spinal cord, where they directly contribute to neuroinflammation.
Thus, the gut
appears to be a key “priming” site for pathogenic T cells, establishing a
mechanistic link between mucosal immunity and CNS inflammation.
A new therapeutic
target to explore
These findings
highlight a critical role for the intestinal epithelial interface in modulating
systemic immune responses. They suggest that the gut environment does not
merely influence immunity but actively participates in the generation of
autoreactive cells involved in MS.
“While current MS
treatments often target B cells, our study highlights the gut as an important
therapeutic target,” emphasized Professor Shohei Suzuki. “Modulating the gut
microbiota or the antigen-presenting activity of intestinal epithelial cells
represents new approaches for treating autoimmune neurological diseases.”
By shedding light on
the gut–brain axis, this study proposes a paradigm shift in the management of
neuroinflammatory diseases. Ultimately, targeting immune interactions at the
level of the intestinal mucosa could help prevent the generation of pathogenic
cells upstream—before they even reach the central nervous system.
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About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.
