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Commensal microbe-derived butyrate epigenetically induces colonic regulatory T cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE49655 | GEO | 2013/11/20

SECONDARY ACCESSION(S): PRJNA214611

REPOSITORIES: GEO

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Commensal microbe-derived butyrate epigenetically induces colonic regulatory T cells

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The commensal-derived metabolite butyrate imprints an antimicrobial program in macrophages

Project description:The balance between tolerogenic and inflammatory responses determines immune homeostasis in the gut. Dysbiosis and a defective host defense against invading intestinal bacteria can shift this balance via bacterial-derived metabolites and trigger chronic inflammation. We show that the short chain fatty acid butyrate modulates monocyte to macrophage differentiation by promoting antimicrobial effector functions. The presence of butyrate modulates antimicrobial activity via a shift in macrophage metabolism and reduction in mTOR activity. This mechanism is furthermore dependent on the inhibitory function of butyrate on histone deacetylase 3 (HDAC3) driving transcription of a set of antimicrobial peptides including calprotectin. The increased antimicrobial activity against several bacterial species is not associated with increased production of conventional cytokines. Butyrate imprints antimicrobial activity of intestinal macrophages in vivo. Our data suggest that commensal bacteria derived butyrate stabilize gut homeostasis by promoting antimicrobial host defense pathways in monocytes that differentiate into intestinal macrophages.

2019-01-30 | GSE111049 | GEO

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