Type I interferons and gut-produced tryptophan chemicals influence brain support cells and nervous system inflammation through a specific receptor

A transcriptional response to type I interferons (IFN-Is) was detected in astrocytes during experimental CNS autoimmunity and in lesions from patients with multiple sclerosis (MS).

• IFN-I signaling in astrocytes is associated with reduced inflammation and lower disease scores in experimental autoimmune encephalomyelitis (EAE).
• The anti-inflammatory effects of nasally administered interferon (IFN)-β may be partly mediated by the aryl hydrocarbon receptor (AHR).
• Dietary tryptophan is converted by gut microbiota into AHR agonists that could limit CNS inflammation through effects on astrocytes.
• Increased EAE scores were observed following ampicillin treatment during recovery, while CNS inflammation decreased in antibiotic-treated mice receiving tryptophan metabolites.
• Circulating levels of AHR agonists were lower in individuals with MS, suggesting a potential link to impaired AHR signaling and CNS inflammation.

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