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.

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Available from: Nicolas Manel, Jul 31, 2015
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    • "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). "
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    • "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]. "
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    • "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. "
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