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Microbiota are dispensable for early stages of de novo regulatory T cell induction within mesenteric lymph nodes

ABSTRACT: Intestinal Foxp3+ regulatory T cell (Treg) subsets are crucial players for tolerance towards microbiota-derived and food-borne antigens, and compelling evidence suggests that intestinal microbiota modulate their differentiation and maintenance. Selected bacterial species and microbiota-derived metabolites such as short-chain fatty acids (SCFAs) have been reported to foster Treg homeostasis in the intestinal lamina propria. Furthermore, gut-draining mesenteric lymph nodes (mLNs) are particularly efficient sites of de novo Treg induction, and we could previously show that mLN stromal cells contribute to this process. Yet, it is not fully elucidated which direct role microbiota and their metabolites play for the early stages of de novo Treg induction and in shaping the Treg transcriptome already during the initial priming within mLNs. Here, we show that neither dysbiotic microbiota nor dietary SCFA supplementation impact de novo induction of Foxp3+ Tregs within mLNs. Even mice housed under germ-free (GF) conditions displayed equivalent frequencies of de novo induced Foxp3+ Tregs within mLNs. Further dissection of the accessible chromatin and transcriptome revealed that microbiota indeed have a limited impact on fostering the establishment of peripherally induced Tregs and do not contribute to the initialization of the epigenetic landscape for an extensive Treg signature. Viewed as a whole, our data suggest that microbiota are dispensable for the early stages of de novo Treg induction within mLNs, while being required to foster further Treg differentiation and homeostasis at later stages within the intestinal lamina propria.

ORGANISM(S): Mus musculus

PROVIDER: GSE150566 | GEO | 2021/03/24

REPOSITORIES: GEO

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