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The microbiota is dispensable for the early stages of peripheral regulatory T cell induction within mesenteric lymph nodes

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Cellular & Molecular Immunology 2021年第5期18卷 1211-1221页

作者： Carolin Wiechers Mangge Zou eric galvez Michael Beckstette Maria Ebel Till Strowig Jochen Huehn Joern Pezoldt Department Experimental Immunology Helmholtz Centre for Infection ResearchBraunschweigGermany Department Microbial Immune Regulation Helmholtz Centre for Infection ResearchBraunschweigGermany Department of Computational Biology for Individualised Medicine Centre for Individualised Infection MedicineHelmholtz Centre for Infection Research and Hannover Medical SchoolHannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical SchoolHannoverGermany Laboratory of Systems Biology and Genetics École Polytechnique Fédérale de LausanneLausanneSwitzerland

Intestinal Foxp3+regulatory T cell(Treg)subsets are crucial players in tolerance to microbiota-derived and food-borne antigens,and compelling evidence suggests that the intestinal microbiota modulates their generation,functional specialization,and maintenance.Selected bacterial species and microbiota-derived metabolites,such as short-chain fatty acids(SCFAs),have been reported to promote Treg homeostasis in the intestinal lamina propria.Furthermore,gut-draining mesenteric lymph nodes(mLNs)are particularly efficient sites for the generation of peripherally induced Tregs(pTregs).Despite this knowledge,the direct role of the microbiota and their metabolites in the early stages of pTreg induction within mLNs is not fully elucidated.Here,using an adoptive transfer-based pTreg induction system,we demonstrate that neither transfer of a dysbiotic microbiota nor dietary SCFA supplementation modulated the pTreg induction capacity of mLNs.Even mice housed under germ-free(GF)conditions displayed equivalent pTreg induction within mLNs.Further molecular characterization of these de novo induced pTregs from mLNs by dissection of their transcriptomes and accessible chromatin regions revealed that the microbiota indeed has a limited impact and does not contribute to the initialization of the Treg-specific epigenetic landscape.Overall,our data suggest that the microbiota is dispensable for the early stages of pTreg induction within mLNs.

关键词： Peripheral regulatory T cells Microbiota Tolerance

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