The microbiota is dispensable for the early stages of peripheral regulatory T cell induction within mesenteric lymph nodes
| Autor: | Jochen Huehn, Joern Pezoldt, Maria Ebel, Till Strowig, Carolin Wiechers, Eric J. C. Gálvez, Mangge Zou, Michael Beckstette |
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| Přispěvatelé: | HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Transcription Genetic Regulatory T cell Immunology Biology T-Lymphocytes Regulatory digestive system Article Epigenesis Genetic Transcriptome 03 medical and health sciences 0302 clinical medicine peripheral regulatory t cells microbiota medicine Animals Immunology and Allergy Mesenteric lymph nodes Mesentery Epigenetics Peripheral regulatory T cells Mice Inbred BALB C tolerance Gene Expression Profiling Microbiota FOXP3 Fatty Acids Volatile Chromatin Gastrointestinal Microbiome Cell biology Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure 030220 oncology & carcinogenesis Peripheral tolerance Dysbiosis Mucosal immunology Female Lymph Nodes Tolerance Homeostasis |
| Zdroj: | Cellular & molecular immunology China Cellular and Molecular Immunology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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