RESUMO
Microbiome-induced interferon signaling through gut-derived natural killer cells is integral to minimize peripheral inflammatory responses in the brain and spinal cord. In a recent issue of Nature, Sanmarco, Wheeler, et al. define how interferon signaling induces LAMP1+TRAIL+ astrocytes, which cause death of inflammatory T cells, mitigating degeneration in a mouse model of demyealination.
Assuntos
Astrócitos/imunologia , Inflamação/imunologia , Linfócitos T/imunologia , Animais , Encéfalo/imunologia , Modelos Animais de Doenças , Interferons/imunologia , Células Matadoras Naturais/imunologia , Camundongos , Transdução de Sinais/imunologia , Medula Espinal/imunologiaRESUMO
Inflammatory bowel disease (IBD) is associated with risk variants in the human genome and dysbiosis of the gut microbiome, though unifying principles for these findings remain largely undescribed. The human commensal Bacteroides fragilis delivers immunomodulatory molecules to immune cells via secretion of outer membrane vesicles (OMVs). We reveal that OMVs require IBD-associated genes, ATG16L1 and NOD2, to activate a noncanonical autophagy pathway during protection from colitis. ATG16L1-deficient dendritic cells do not induce regulatory T cells (T(regs)) to suppress mucosal inflammation. Immune cells from human subjects with a major risk variant in ATG16L1 are defective in T(reg) responses to OMVs. We propose that polymorphisms in susceptibility genes promote disease through defects in "sensing" protective signals from the microbiome, defining a potentially critical gene-environment etiology for IBD.
