Abstract

SummaryA reciprocal interaction exists between the gut microbiota and the immune system. Regulatory T (Treg) cells are important for controlling immune responses and for maintaining the intestinal homeostasis but their precise influence on the gut microbiota is unclear. We studied the effects of Treg cell depletion on inflammation of the intestinal mucosa and analysed the gut microbiota before and after depletion of Treg cells using the DEpletion of REGulatory T cells (DEREG) mouse model. DNA was extracted from stool samples of DEREG mice and wild‐type littermates at different time‐points before and after diphtheria toxin application to deplete Treg cells in DEREG mice. The V3/V4 region of the 16S rRNA gene was used for studying the gut microbiota with Illumina MiSeq paired ends sequencing. Multidimensional scaling separated the majority of gut microbiota samples from late time‐points after Treg cell depletion in DEREG mice from samples of early time‐points before Treg cell depletion in these mice and from gut microbiota samples of wild‐type mice. Treg cell depletion in DEREG mice was accompanied by an increase in the relative abundance of the phylum Firmicutes and by intestinal inflammation in DEREG mice 20 days after Treg cell depletion, indicating that Treg cells influence the gut microbiota composition. In addition, the variables cage, breeding and experiment number were associated with differences in the gut microbiota composition and these variables should be respected in murine studies.

Highlights

  • The intestine contains a high abundance of forkhead box protein 3-positive (Foxp3+) regulatory T (Treg) cells

  • We studied the effects of Treg cell depletion on inflammation of the intestinal mucosa and analysed the gut microbiota before and after depletion of Treg cells using the DEpletion of REGulatory T cells (DEREG) mouse model

  • Treg cell depletion in DEREG mice was accompanied by an increase in the relative abundance of the phylum Firmicutes and by intestinal inflammation in DEREG mice 20 days after Treg cell depletion, indicating that Treg cells influence the gut microbiota composition

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Summary

Introduction

The intestine contains a high abundance of forkhead box protein 3-positive (Foxp3+) regulatory T (Treg) cells. They are fundamental for maintaining intestinal homeostasis by controlling immune responses of the innate and adaptive immune system.[1] Loss-of-function mutations within FOXP3, the master transcription factor of Treg cells, occur in the IPEX (Immune dysregulation polyendocrinopathy enteropathy X-linked) syndrome in humans, a fatal autoimmune disease with severe enteropathy, which is an early organ manifestation and a hallmark of the disease.[2] The majority of Treg cells are derived from the thymus, but they can be induced. Immunology published by John Wiley & Sons Ltd., Immunology, 159, 344–353. Short-chain fatty acids, fermentation products of commensal gut microbiota in the colon, in particular butyrate, were shown to regulate the Treg cell network by promoting the induction and fitness of Treg cells.[6,7,8]

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