Nature Communications · 10 authors, 5 centres
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This preclinical study using mouse models and in vitro cell culture demonstrates that microbiota-derived pentanoate promotes intracellular iron uptake in intestinal regulatory T cells via HIF-2α and c-Maf, which is critical for their differentiation and the maintenance of immune tolerance in the intestine.
The central finding is that intestinal regulatory T cell (Treg) differentiation and function are stringently dependent on high intracellular iron levels, which promote the expression of HIF-2α and c-Maf. These iron levels are facilitated by the microbiota metabolite pentanoate. Supplementation with either iron or pentanoate rescued defects in intestinal Tregs in microbiota-depleted mice. Limitations include that the findings are derived from preclinical mouse models, which may not fully recapitulate the heterogeneity of human IBD, and the direct therapeutic implications for humans require further investigation. The work suggests a mechanistic pathway where microbiota-derived nutrients influence immune cell homeostasis.
