scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria

TL;DR: The authors showed that colonisation of mice with a segmented filamentous bacterium (SFB) is sufficient to induce the appearance of CD4+ T helper cells that produce IL-17 and IL-22 (Th17 cells) in the lamina propria.
About: This article is published in Cell.The article was published on 2009-10-30 and is currently open access. It has received 3860 citations till now. The article focuses on the topics: Segmented filamentous bacteria & Immune system.
Citations
More filters
Journal ArticleDOI
19 Dec 2013-Nature
TL;DR: It is shown that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice and ameliorated the development of colitis induced by adoptive transfer of CD4+ CD45RBhi T cells in Rag1−/− mice.
Abstract: Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.

3,596 citations


Cites background from "Induction of Intestinal Th17 Cells ..."

  • ...Naive CD4(1) T cells were cultured under Treg-cell-inducing condition in the absence (2) or presence (1) of butyrate....

    [...]

Journal ArticleDOI
08 Jun 2012-Science
TL;DR: Advances in understanding of the interactions between resident microbes and the immune system are reviewed and the implications for human health are reviewed.
Abstract: The large numbers of microorganisms that inhabit mammalian body surfaces have a highly coevolved relationship with the immune system. Although many of these microbes carry out functions that are critical for host physiology, they nevertheless pose the threat of breach with ensuing pathologies. The mammalian immune system plays an essential role in maintaining homeostasis with resident microbial communities, thus ensuring that the mutualistic nature of the host-microbial relationship is maintained. At the same time, resident bacteria profoundly shape mammalian immunity. Here, we review advances in our understanding of the interactions between resident microbes and the immune system and the implications of these findings for human health.

3,330 citations

Journal ArticleDOI
27 Mar 2014-Cell
TL;DR: In high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses.

3,257 citations


Cites background from "Induction of Intestinal Th17 Cells ..."

  • ...Aside from the direct influence of the microbiota on the immune machinery associated with the induction of oral tolerance, commensalspecific Treg can promote class switching to IgA in an antigenspecific manner (Cong et al., 2009; Tsuji et al., 2009), thereby controlling the host relationship with the microbiota via multiple mechanisms (Peterson et al., 2007; Suzuki et al., 2004) (Figure 2)....

    [...]

  • ...Indeed, established IgA-producing clones are outcompeted by novel antibacterial responses, allowing the mucosal immune system to respond to a constantly changing microbiota (Hapfelmeier et al., 2010)....

    [...]

  • ...IgA specific for commensals is produced with the help of intestinal dendritic cells that sample commensals associated with the epithelium and interact with B and T cells in the Peyer’s patches to produce IgA specific for commensal-derived antigens (Macpherson and Uhr, 2004)....

    [...]

  • ...Compartmentalization of intestinal bacteria also depends on secreted immunoglobulin A (IgA)....

    [...]

  • ...Indeed, colostrum and breast milk contain live microbes, metabolites, IgA, and immune cells as well as cytokines....

    [...]

Journal ArticleDOI
19 Dec 2013-Nature
TL;DR: The results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.
Abstract: Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. We found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of Treg cells. A boost in Treg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.

3,164 citations

Journal ArticleDOI
21 Jan 2011-Science
TL;DR: Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.
Abstract: CD4+ T regulatory cells (Tregs), which express the Foxp3 transcription factor, play a critical role in the maintenance of immune homeostasis. Here, we show that in mice, Tregs were most abundant in the colonic mucosa. The spore-forming component of indigenous intestinal microbiota, particularly clusters IV and XIVa of the genus Clostridium, promoted Treg cell accumulation. Colonization of mice by a defined mix of Clostridium strains provided an environment rich in transforming growth factor–β and affected Foxp3+ Treg number and function in the colon. Oral inoculation of Clostridium during the early life of conventionally reared mice resulted in resistance to colitis and systemic immunoglobulin E responses in adult mice, suggesting a new therapeutic approach to autoimmunity and allergy.

3,096 citations

References
More filters
Journal ArticleDOI
TL;DR: By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.
Abstract: DAVID bioinformatics resources consists of an integrated biological knowledgebase and analytic tools aimed at systematically extracting biological meaning from large gene/protein lists. This protocol explains how to use DAVID, a high-throughput and integrated data-mining environment, to analyze gene lists derived from high-throughput genomic experiments. The procedure first requires uploading a gene list containing any number of common gene identifiers followed by analysis using one or more text and pathway-mining tools such as gene functional classification, functional annotation chart or clustering and functional annotation table. By following this protocol, investigators are able to gain an in-depth understanding of the biological themes in lists of genes that are enriched in genome-scale studies.

31,015 citations


"Induction of Intestinal Th17 Cells ..." refers methods in this paper

  • ...For enrichment analysis of biological process ontology, probe lists were analyzed in DAVID (Dennis et al., 2003; Huang da et al., 2009) and processes were selected based on p values smaller than 0.01....

    [...]

Journal ArticleDOI
21 Dec 2006-Nature
TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
Abstract: The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.

10,126 citations


"Induction of Intestinal Th17 Cells ..." refers background in this paper

  • ...488 Cell 139, 485–498, October 30, 2009 ª2009 Elsevier Inc....

    [...]

  • ...Error bars represent the SD. 492 Cell 139, 485–498, October 30, 2009 ª2009 Elsevier Inc. Turnbaugh et al., 2006), but they also have profound effects on the host immune system (Cash et al., 2006; Macpherson and Harris, 2004)....

    [...]

  • ...Error bars represent the SD. Cell 139, 485–498, October 30, 2009 ª2009 Elsevier Inc. 491 growth of C. rodentium than were noncohoused mice, as demonstrated by recovery of infectious units from the wall of the colon (Figure 7A)....

    [...]

  • ...Error bars represent the SD. Cell 139, 485–498, October 30, 2009 ª2009 Elsevier Inc. 489 (Figure 5B)....

    [...]

  • ...Cell 139, 485–498, October 30, 2009 ª2009 Elsevier Inc. 487 intentionally introduced into Jackson Laboratory animals....

    [...]

Journal ArticleDOI
TL;DR: DAMID is a web-accessible program that integrates functional genomic annotations with intuitive graphical summaries that assists in the interpretation of genome-scale datasets by facilitating the transition from data collection to biological meaning.
Abstract: The distributed nature of biological knowledge poses a major challenge to the interpretation of genome-scale datasets, including those derived from microarray and proteomic studies. This report describes DAVID, a web-accessible program that integrates functional genomic annotations with intuitive graphical summaries. Lists of gene or protein identifiers are rapidly annotated and summarized according to shared categorical data for Gene Ontology, protein domain, and biochemical pathway membership. DAVID assists in the interpretation of genome-scale datasets by facilitating the transition from data collection to biological meaning.

8,849 citations

Journal ArticleDOI
14 Feb 2003-Science
TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
Abstract: Regulatory T cells engage in the maintenance of immunological self-tolerance by actively suppressing self-reactive lymphocytes. Little is known, however, about the molecular mechanism of their development. Here we show that Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells. Furthermore, retroviral gene transfer of Foxp3 converts naive T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+ regulatory T cells. Thus, Foxp3 is a key regulatory gene for the development of regulatory T cells.

8,082 citations


"Induction of Intestinal Th17 Cells ..." refers background in this paper

  • ...…growth factor b (TGF-b) for their differentiation and are defined by the expression of the lineage-specific transcription factors RORgt and Foxp3, respectively (Fontenot et al., 2003; Hori et al., 2003; Ivanov et al., 2006; Khattri et al., 2003; Mangan et al., 2006; Veldhoen et al., 2006)....

    [...]

  • ...Th17 and Treg cells are both dependent on transforming growth factor b (TGF-b) for their differentiation and are defined by the expression of the lineage-specific transcription factors RORgt and Foxp3, respectively (Fontenot et al., 2003; Hori et al., 2003; Ivanov et al., 2006; Khattri et al., 2003; Mangan et al., 2006; Veldhoen et al., 2006)....

    [...]

Journal ArticleDOI
TL;DR: It is reported that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development and function and ectopic expression ofFoxp3 confers suppressor function on peripheral CD4-CD25− T cells.
Abstract: CD4+CD25+ regulatory T cells are essential for the active suppression of autoimmunity. Here we report that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development. The lethal autoimmune syndrome observed in Foxp3-mutant scurfy mice and Foxp3-null mice results from a CD4+CD25+ regulatory T cell deficiency and not from a cell-intrinsic defect of CD4+CD25- T cells. CD4+CD25+ regulatory T cells rescue disease development and preferentially expand when transferred into neonatal Foxp3-deficient mice. Furthermore, ectopic expression of Foxp3 confers suppressor function on peripheral CD4+CD25- T cells. Thus, Foxp3 is a critical regulator of CD4+CD25+ regulatory T cell development and function.

7,321 citations


"Induction of Intestinal Th17 Cells ..." refers background in this paper

  • ...…growth factor b (TGF-b) for their differentiation and are defined by the expression of the lineage-specific transcription factors RORgt and Foxp3, respectively (Fontenot et al., 2003; Hori et al., 2003; Ivanov et al., 2006; Khattri et al., 2003; Mangan et al., 2006; Veldhoen et al., 2006)....

    [...]

  • ...Th17 and Treg cells are both dependent on TGF-β for their differentiation and are defined by the expression of the lineage-specific transcription factors RORγt and Foxp3, respectively (Fontenot et al., 2003; Hori et al., 2003; Ivanov et al., 2006; Khattri et al., 2003; Mangan et al., 2006)(Veldhoen et al....

    [...]

Related Papers (5)