Dataset Information

Depletion of Foxp3⁺ regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.

ABSTRACT: A 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.

SUBMITTER: Kehrmann J

PROVIDER: S-EPMC7011623 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Depletion of Foxp3<sup>+</sup> regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.

Kehrmann Jan J Effenberg Laura L Wilk Camilla C Schoemer Davina D Ngo Thi Phuong Nhi N Adamczyk Alexandra A Pastille Eva E Scholtysik René R Klein-Hitpass Ludger L Klopfleisch Robert R Westendorf Astrid M AM Buer Jan J

Immunology 20191212 3

A 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 extra ...[more]

PMID: 31755554

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Project description:Type 1 diabetes (T1D) represents a hallmark of the fatal multiorgan autoimmune syndrome affecting humans with abrogated Foxp3+ regulatory T (Treg) cell function due to Foxp3 gene mutations, but whether the loss of Foxp3+ Treg cell activity is indeed sufficient to promote β cell autoimmunity requires further scrutiny. As opposed to human Treg cell deficiency, β cell autoimmunity has not been observed in non-autoimmune-prone mice with constitutive Foxp3 deficiency or after diphtheria toxin receptor (DTR)-mediated ablation of Foxp3+ Treg cells. In the spontaneous nonobese diabetic (NOD) mouse model of T1D, constitutive Foxp3 deficiency did not result in invasive insulitis and hyperglycemia, and previous studies on Foxp3+ Treg cell ablation focused on Foxp3DTR NOD mice, in which expression of a transgenic BDC2.5 T cell receptor (TCR) restricted the CD4+ TCR repertoire to a single diabetogenic specificity. Here we revisited the effect of acute Foxp3+ Treg cell ablation on β cell autoimmunity in NOD mice in the context of a polyclonal TCR repertoire. For this, we took advantage of the well-established DTR/GFP transgene of DEREG mice, which allows for specific ablation of Foxp3+ Treg cells without promoting catastrophic autoimmune diseases. We show that the transient loss of Foxp3+ Treg cells in prediabetic NOD.DEREG mice is sufficient to precipitate severe insulitis and persistent hyperglycemia within 5 days after DT administration. Importantly, DT-treated NOD.DEREG mice preserved many clinical features of spontaneous diabetes progression in the NOD model, including a prominent role of diabetogenic CD8+ T cells in terminal β cell destruction. Despite the severity of destructive β cell autoimmunity, anti-CD3 mAb therapy of DT-treated mice interfered with the progression to overt diabetes, indicating that the novel NOD.DEREG model can be exploited for preclinical studies on T1D under experimental conditions of synchronized, advanced β cell autoimmunity. Overall, our studies highlight the continuous requirement of Foxp3+ Treg cell activity for the control of genetically pre-installed autoimmune diabetes.

Dataset Information

Depletion of Foxp3⁺ regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.

Publications

Depletion of Foxp3<sup>+</sup> regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Depletion of Foxp3+ regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.

Publications

Depletion of Foxp3<sup>+</sup> regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Depletion of Foxp3⁺ regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.