The gut microbiota-induced kynurenic acid recruits GPR35-positive macrophages to promote experimental encephalitis

The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4+ T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesis of kynurenic acid (KYNA), which modulates the recruitment and aggregation of GPR35-positive macrophages. Subsequently, a robust T helper 17 (Th17) immune response is activated, ultimately triggering the onset of EAE. Conversely, modulating the KYNA-mediated GPR35 signaling in Cx3cr1+ macrophages leads to a remarkable amelioration of EAE. These findings shed light on the crucial role of microbial-derived tryptophan metabolites in regulating immune responses within extraintestinal tissues.

Automated summary

The complex interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) is not well understood. This study reveals the similarities between CD4+ T cells in the spinal cord and the small intestine. The collaboration between the microbiota, especially those enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells leads to the biosynthesis of kynurenic acid (KYNA), which triggers a Th17 immune response and the onset of EAE.