Functional specialization of gut CD103^+ dendritic cells in the regulation of tissue-selective T cell homing
Bengt Johansson-Lindbom,Marcus Svensson,Oliver Pabst,Caroline Palmqvist,Gabriel Márquez,Reinhold Förster,William W. Agace +6 more
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Results demonstrate a unique function for LP-derived CD103+ MLN DCs in the generation of gut-tropic effector T cells in vitro.Abstract:
Gut-associated lymphoid tissue (GALT) dendritic cells (DCs) display a unique ability to generate CCR9 + α 4 β 7 + gut-tropic CD8 + effector T cells. We demonstrate efficient induction of CCR9 and α 4 β 7 on CD8 + T cells in mesenteric lymph nodes (MLNs) after oral but not intraperitoneal (i.p.) antigen administration indicating differential targeting of DCs via the oral route. In vitro, lamina propria (LP)–derived DCs were more potent than MLN or Peyer's patch DCs in their ability to generate CCR9 + α 4 β 7 + CD8 + T cells. The integrin α chain CD103 ( α E) was expressed on almost all LP DCs, a subset of MLN DCs, but on few splenic DCs. CD103 + MLN DCs were reduced in number in CCR7 − / − mice and, although CD8 + T cells proliferated in the MLNs of CCR7 − / − mice after i.p. but not oral antigen administration, they failed to express CCR9 and had reduced levels of α 4 β 7. Strikingly, although CD103 + and CD103 − MLN DCs were equally potent at inducing CD8 + T cell proliferation and IFN- γ production, only CD103 + DCs were capable of generating gut-tropic CD8 + effector T cells in vitro. Collectively, these results demonstrate a unique function for LP-derived CD103 + MLN DCs in the generation of gut-tropic effector T cells.read more
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A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism
Janine L. Coombes,Karima R.R. Siddiqui,Carolina V. Arancibia-Cárcamo,Jason A. Hall,Cheng-Ming Sun,Yasmine Belkaid,Fiona Powrie +6 more
TL;DR: It is shown that after antigen activation in the intestine, naive T cells acquire expression of Foxp3, and RA is identified as a cofactor in T reg cell generation, providing a mechanism via which functionally specialized gut-associated lymphoid tissue DCs can extend the repertoire of T reg cells focused on the intestine.
Journal ArticleDOI
Intestinal epithelial cells: regulators of barrier function and immune homeostasis
Lance W. Peterson,David Artis +1 more
TL;DR: This Review provides a comprehensive overview of how IECs maintain host–commensal microbial relationships and immune cell homeostasis in the intestine.
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Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid
Cheng-Ming Sun,Jason A. Hall,Jason A. Hall,Rebecca Blank,Nicolas Bouladoux,Mohamed Oukka,J. Rodrigo Mora,Yasmine Belkaid +7 more
TL;DR: It is shown that peripheral conversion of CD4+ T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment, and that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion.
Journal ArticleDOI
CCR7 and its ligands: balancing immunity and tolerance
TL;DR: This work focuses on the cellular and molecular mechanisms that enable CCR7 and its two ligands, CCL19 and CCL21, to balance immunity and tolerance.
Journal ArticleDOI
Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses.
TL;DR: A population of CD11b+F4/80+CD11c− macrophages in the lamina propria that expressed several anti-inflammatory molecules, including interleukin 10 (IL-10), but little or no proinflammatory cytokines, even after stimulation with Toll-like receptor ligands is described.
References
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CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.
Reinhold Förster,Andreas Schubel,Dagmar Breitfeld,Elisabeth Kremmer,Ingrid Renner-Müller,Eckhard Wolf,Martin Lipp +6 more
TL;DR: In this paper, the chemokine receptor CCR7 was identified as an important organizer of the primary immune response in mice, and severely delayed kinetics regarding the antibody response and lack contact sensitivity and delayed type hypersensitivity reactions.
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Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo.
TL;DR: The naïve and memory T lymphocyte pools are maintained through poorly understood homeostatic mechanisms that may include signaling via cytokine receptors, and shows that interleukin-7 (IL-7) plays multiple roles in regulating homeostasis of CD8+ T cells.
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Retinoic Acid Imprints Gut-Homing Specificity on T Cells
TL;DR: Vitamin A deficiency caused a reduction in alpha4beta7(+) memory/activated T cells in lymphoid organs and a depletion of T cells from the intestinal lamina propria, and revealed a novel role for retinoic acid in the imprinting of gut-homing specificity on T cells.
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Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?
Manfred B. Lutz,Gerold Schuler +1 more
TL;DR: Closer inspection reveals that tolerance is observed when partial- or semi-maturation of DCs occurs, whereas only full DC maturation is immunogenic, and the decisive immunogenic signal seems to be the release of proinflammatory cytokines from the DCs.
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Potent and Selective Stimulation of Memory-Phenotype CD8+ T Cells In Vivo by IL-15
TL;DR: It is shown here that, unlike IL-2, IL-15 closely mimics the effects of IFN I in causing strong and selective stimulation of memory-phenotype CD44hi CD8+ (but not CD4+) cells in vivo; similar specificity applies to purified T cells in vitro and correlates with much higher expression of IL- 2Rbeta onCD8+ cells than on CD4+ cells.