Specific Microbiota Direct the Differentiation of IL-17-Producing T-Helper Cells in the Mucosa of the Small Intestine

Kimmel Center for Biology and Medicine of the Skirball Institute, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Cell host & microbe (Impact Factor: 12.33). 11/2008; 4(4):337-49. DOI: 10.1016/j.chom.2008.09.009
Source: PubMed


The requirements for in vivo steady state differentiation of IL-17-producing T-helper (Th17) cells, which are potent inflammation effectors, remain obscure. We report that Th17 cell differentiation in the lamina propria (LP) of the small intestine requires specific commensal microbiota and is inhibited by treating mice with selective antibiotics. Mice from different sources had marked differences in their Th17 cell numbers and animals lacking Th17 cells acquired them after introduction of bacteria from Th17 cell-sufficient mice. Differentiation of Th17 cells correlated with the presence of cytophaga-flavobacter-bacteroidetes (CFB) bacteria in the intestine and was independent of toll-like receptor, IL-21 or IL-23 signaling, but required appropriate TGF-beta activation. Absence of Th17 cell-inducing bacteria was accompanied by increase in Foxp3+ regulatory T cells (Treg) in the LP. Our results suggest that composition of intestinal microbiota regulates the Th17:Treg balance in the LP and may thus influence intestinal immunity, tolerance, and susceptibility to inflammatory bowel diseases.

Download full-text


Available from: Nicolas Manel, Jul 31, 2015
  • Source
    • "Additionally, despite the incomplete transfer of GM, this method has been used extensively and to great effect. While a lack of phenotype transfer between cohoused mice does not necessarily obviate a contribution of the GM to the phenotype, positive transmission of the phenotype between cohoused mice provides strong support for a microbial influence (Bel et al. 2014; Ivanov et al. 2008; Vijay-Kumar et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Eukaryotic organisms are colonized by rich and dynamic communities of microbes, both internally (e.g., in the gastrointestinal and respiratory tracts) and externally (e.g., on skin and external mucosal surfaces). The vast majority of bacterial microbes reside in the lower gastrointestinal (GI) tract, and it is estimated that the gut of a healthy human is home to some 100 trillion bacteria, roughly an order of magnitude greater than the number of host somatic cells. The development of culture-independent methods to characterize the gut microbiota (GM) has spurred a renewed interest in its role in host health and disease. Indeed, associations have been identified between various changes in the composition of the GM and an extensive list of diseases, both enteric and systemic. Animal models provide a means whereby causal relationships between characteristic differences in the GM and diseases or conditions can be formally tested using genetically identical animals in highly controlled environments. Clearly, the GM and its interactions with the host and myriad environmental factors are exceedingly complex, and it is rare that a single microbial taxon associates with, much less causes, a phenotype with perfect sensitivity and specificity. Moreover, while the exact numbers are the subject of debate, it is well recognized that only a minority of gut bacteria can be successfully cultured ex vivo. Thus, to perform studies investigating causal roles of the GM in animal model phenotypes, researchers need clever techniques to experimentally manipulate the GM of animals, and several ingenious methods of doing so have been developed, each providing its own type of information and with its own set of advantages and drawbacks. The current review will focus on the various means of experimentally manipulating the GM of research animals, drawing attention to the factors that would aid a researcher in selecting an experimental approach, and with an emphasis on mice and rats, the primary model species used to evaluate the contribution of the GM to a disease phenotype. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email:
    Full-text · Article · Aug 2015 · ILAR journal / National Research Council, Institute of Laboratory Animal Resources
  • Source
    • "Intestinal microbiota interact with the host digestive and immune systems [5], provides positive or negative effects on the health of the host [6]. The positive effects of gut microbiota including playing a pivotal role in nutrient digestion and energy recovery, as a source of vitamins [7], SCFA (especially butyrate) production [5], protect the intestine against colonization by exogenous pathogens [8], and regulating the balance and homeostasis of different helper T cell populations in the lamina propria and further emphasize the critical role that the microbiota play in the development of the immune system [4]. Protective effects of commensal bifidobacteria were attributed primarily to the production of acetate that improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lactobacillus plantarum Dad-13 that isolated from “dadih” (traditional Indonesian fermented milk) has been known as probiotic, while sweet potato fiber has been proven as an effective prebiotic. The objective of this study was to evaluate the potency of Lactobacillus plantarum Dad-13 and sweet potato fiber as immunomodulators in terms of intestinal secretory immunoglobulin A (sIgA) and splenocyte gamma-interferon (IFN-􏰀). Sixty male Sprague Dawley rats (uninfected and infected) were divided into five groups: AIN-93, Indonesian children diet (ICD), Sweet potato fiber (SPF), SPF + Lactobacillus plantarum Dad-13 (SPFL), and fructooligosaccharides + Lacto-B (FOSL). After diet intervention, the rats were killed and sampled including intestinal fluid, spleen and caecal digesta. The results showed that soluble fiber such as sweet potato fiber could not increase the number of lactobacilli in infected rats, but could play a role in mucosal immune response through the increasing of sIgA. While, Lactobacillus plantarum Dad-13 contained in the combination with sweet potato fiber may has potency in systemic immune stimulation, because of the tendency to increase level of splenocyte IFN-􏰀 in infected rats.
    Full-text · Article · Feb 2015
  • Source
    • "The development and function of the mammalian immune system is dependent upon signals conveyed by the microbiota (Belkaid and Hand, 2014; Hooper et al., 2012; Kamada et al., 2013). In particular, the abundance and type of T lymphocytes in the gut is severely reduced in germ-free (GF) mice (Atarashi et al., 2011; Ivanov et al., 2008; Mazmanian et al., 2005; Round and Mazmanian, 2010). While T cell activation is governed by ligation of the T cell receptor (TCR), the quality and nature of the response is dependent on secondary signals such as the cytokine milieu. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Altered commensal communities are associated with human disease. IgA mediates intestinal homeostasis and regulates microbiota composition. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers. However, the pathways directing host IgA responses toward the microbiota remain unknown. Here, we report that signaling through the innate adaptor MyD88 in gut T cells coordinates germinal center responses, including TFH and IgA+ B cell development. TFH development is deficient in germ-free mice and can be restored by feeding TLR2 agonists that activate T cell-intrinsic MyD88 signaling. Loss of this pathway diminishes high-affinity IgA targeting of the microbiota and fails to control the bacterial community, leading to worsened disease. Our findings identify that T cells converge innate and adaptive immune signals to coordinate IgA against the microbiota, constraining microbial community membership to promote symbiosis. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Jan 2015 · Cell Host & Microbe
Show more