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Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Updated: Jan 17, 2026

Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation
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Gut-derived metabolites drive Th17 cell pathogenicity in multiple sclerosis.

J Rebeaud1, S Vigne1, V Bressoud1

  • 1Laboratories of Neuroimmunology, Center for Research in Neuroscience and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, and University of Lausanne, Lausanne, Switzerland.

Cell Reports
|September 21, 2025
PubMed
Summary

Gut bacteria metabolites influence multiple sclerosis (MS) progression. Indole-3-carboxylate (I3CA), a gut microbe product, exacerbates EAE in mice and correlates with MS severity in humans, suggesting therapeutic targets.

Keywords:
CP: MetabolismCP: NeuroscienceTh17 lymphocytesblood biomarkerexperimental autoimmune encephalomyelitisgut-brain axisindole derivativesmicrobiota-derived metabolitesmultiple sclerosisneuroinflammation

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Area of Science:

  • Neuroimmunology
  • Microbiome research
  • Metabolomics

Background:

  • The gut-brain axis is increasingly recognized for its role in multiple sclerosis (MS) pathogenesis.
  • Mechanisms linking the gut environment to MS and therapeutic strategies remain unclear.

Purpose of the Study:

  • To investigate how the gut environment, specifically microbiota-derived metabolites, influences the pathogenicity of myelin-specific Th17 cells in the context of MS.

Main Methods:

  • Utilized the adoptive Th17 cell transfer experimental autoimmune encephalomyelitis (EAE) mouse model.
  • Administered antibiotics to disrupt the intestinal microbiome and analyzed fecal filtrates.
  • Performed fecal metabolomic profiling and oral supplementation with indole-3-carboxylate (I3CA).
  • Assessed disease severity in mice and correlated I3CA levels with neurofilament light chain in persons with MS (PwMS).

Main Results:

  • Antibiotic treatment reduced pathogenic Th17 cell signatures in the colon.
  • Fecal filtrates enhanced myelin-specific Th17 cell encephalitogenic properties in vitro and in vivo.
  • Identified altered tryptophan-derived metabolites, notably I3CA, in fecal samples.
  • Oral I3CA supplementation accelerated EAE development in mice.
  • Elevated blood I3CA levels in PwMS correlated with increased disease severity and serum neurofilament light chain.

Conclusions:

  • Microbiota-derived metabolites play a critical role in gut-mediated neuroinflammation relevant to MS.
  • Indole-3-carboxylate (I3CA) emerges as a key metabolite influencing disease pathogenicity.
  • These findings offer potential therapeutic avenues targeting the gut-brain axis for MS management.