title: Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria.
abstract: Tolerance to food antigen manifests in the absence and/or suppression of antigen-specific immune responses locally in the gut but also systemically, a phenomenon known as oral tolerance. Oral tolerance is thought to originate in the gut-draining lymph nodes, which support the generation of FoxP3(+) regulatory T (Treg) cells. Here we use several mouse models to show that Treg cells, after their generation in lymph nodes, need to home to the gut to undergo local expansion to install oral tolerance. Proliferation of Treg cells in the intestine and production of interleukin-10 by gut-resident macrophages was blunted in mice deficient in the chemokine (C-X3-C motif) receptor 1 (CX3CR1). We propose a model of stepwise oral tolerance induction comprising the generation of Treg cells in the gut-draining lymph nodes, followed by migration into the gut and subsequent expansion of Treg cells driven by intestinal macrophages.
authors.affiliation: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors.forename: Usriansyah
authors.initials: U
authors.lastname: Hadis
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wahl
authors.forename: Olga
authors.initials: O
authors.lastname: Schulz
authors.forename: Matthias
authors.initials: M
authors.lastname: Hardtke-Wolenski
authors.forename: Angela
authors.initials: A
authors.lastname: Schippers
authors.forename: Norbert
authors.initials: N
authors.lastname: Wagner
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabst
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002455:Cell Division; D002634:Chemotaxis, Leukocyte; D003967:Diarrhea / Q000209:etiology / Q000276:immunology; D005512:Food Hypersensitivity / Q000150:complications / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000172:deficiency; D007108:Immune Tolerance / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000166:cytology* / Q000276:immunology; D010047:Ovalbumin / Q000633:toxicity; D019707:Receptors, Chemokine / Q000172:deficiency; D016201:Receptors, Lymphocyte Homing; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D016753:Interleukin-10; D010047:Ovalbumin