79
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Oral tolerance to food protein

      review-article
      1 , * ,   2 , *
      Mucosal Immunology
      Nature Publishing Group

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Oral tolerance is the state of local and systemic immune unresponsiveness that is induced by oral administration of innocuous antigen such as food proteins. An analogous but more local process also regulates responses to commensal bacteria in the large intestine and, together, mucosally induced tolerance appears to prevent intestinal disorders such as food allergy, celiac disease, and inflammatory bowel diseases. Here we discuss the anatomical basis of antigen uptake and recognition in oral tolerance and highlight possible mechanisms underlying the immunosuppression. We propose a model of stepwise induction of oral tolerance in which specialized populations of mucosal dendritic cells and the unique microenvironment of draining mesenteric lymph nodes combine to generate regulatory T cells that undergo subsequent expansion in the small intestinal lamina propria. The local and systemic effects of these regulatory T cells prevent potentially dangerous hypersensitivity reactions to harmless antigens derived from the intestine and hence are crucial players in immune homeostasis.

          Related collections

          Most cited references68

          • Record: found
          • Abstract: found
          • Article: not found

          CCR7 and its ligands: balancing immunity and tolerance.

          A key feature of the immune system is its ability to induce protective immunity against pathogens while maintaining tolerance towards self and innocuous environmental antigens. Recent evidence suggests that by guiding cells to and within lymphoid organs, CC-chemokine receptor 7 (CCR7) essentially contributes to both immunity and tolerance. This receptor is involved in organizing thymic architecture and function, lymph-node homing of naive and regulatory T cells via high endothelial venules, as well as steady state and inflammation-induced lymph-node-bound migration of dendritic cells via afferent lymphatics. Here, we focus on the cellular and molecular mechanisms that enable CCR7 and its two ligands, CCL19 and CCL21, to balance immunity and tolerance.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria.

            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. Copyright © 2011 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Origin of the lamina propria dendritic cell network.

              CX(3)CR1(+) and CD103(+) dendritic cells (DCs) in intestinal lamina propria play a key role in mucosal immunity. However, the origin and the developmental pathways that regulate their differentiation in the lamina propria remain unclear. We showed that monocytes gave rise exclusively to CD103(-)CX(3)CR1(+) lamina propria DCs under the control of macrophage-colony-stimulating factor receptor (M-CSFR) and Fms-like thyrosine kinase 3 (Flt3) ligands. In contrast, common DC progenitors (CDP) and pre-DCs, which give rise to lymphoid organ DCs but not to monocytes, differentiated exclusively into CD103(+)CX(3)CR1(-) lamina propria DCs under the control of Flt3 and granulocyte-macrophage-colony-stimulating factor receptor (GM-CSFR) ligands. CD103(+)CX(3)CR1(-) DCs but not CD103(-)CX(3)CR1(+) DCs in the lamina propria constitutively expressed CCR7 and were the first DCs to transport pathogenic Salmonella from the intestinal tract to the mesenteric lymph nodes. Altogether, these results underline the diverse origin of the lamina propria DC network and identify mucosal DCs that arise from pre-DCs as key sentinels of the gut immune system.
                Bookmark

                Author and article information

                Journal
                Mucosal Immunol
                Mucosal Immunol
                Mucosal Immunology
                Nature Publishing Group
                1933-0219
                1935-3456
                May 2012
                08 February 2012
                : 5
                : 3
                : 232-239
                Affiliations
                [1 ]simpleInstitute of Immunology, Hannover Medical School , Hannover, Germany
                [2 ]simpleInstitute of Infection, Immunity and Inflammation, University of Glasgow , Glasgow, Scotland
                Author notes
                Article
                mi20124
                10.1038/mi.2012.4
                3328017
                22318493
                f03ec9e2-774a-4ea5-8323-4e26252ec692
                Copyright © 2012 Society for Mucosal Immunology

                This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

                History
                : 13 December 2011
                : 02 January 2012
                Categories
                Review

                Immunology
                Immunology

                Comments

                Comment on this article