11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Combined Blockade of the Histamine H1 and H4 Receptor Suppresses Peanut-Induced Intestinal Anaphylaxis by Regulating Dendritic Cell Function

      research-article
      , MD, PhD, , PhD, , BS, , MD, PhD, , PhD, , MD
      Allergy
      H4R, H1R, peanut allergy, dendritic cells, CD4+ T cells

      Read this article at

      ScienceOpenPublisherPMC
      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

          Background

          Signaling through histamine receptors on dendritic cells (DCs) may be involved in the effector phase of peanut-induced intestinal anaphylaxis.

          Objectives

          To determine the role of histamine H1 (H1R) and H4 receptors (H4R) in intestinal allergic responses in a model of peanut allergy.

          Methods

          Balb/c mice were sensitized and challenged to peanut. During the challenge phase, mice were treated orally with the H1R antagonist, loratadine, and/or the H4R antagonist, JNJ7777120. Bone marrow-derived DCs (BMDCs) were adoptively transferred to non-sensitized WT mice. Symptoms, intestinal inflammation, mesenteric lymph node and intestine mucosal DCs were assessed. Effects of the drugs on DC chemotaxis, calcium mobilization, and antigen-presenting cell function were measured.

          Results

          Treatment with loratadine or JNJ7777120 individually partially suppressed development of diarrhea and intestinal inflammation and decreased the numbers of DCs in the mesenteric lymph nodes and lamina propria. Combined treatment with both drugs prevented development of diarrhea and intestinal inflammation. In vitro, the combination suppressed DC antigen presenting cell function to T helper cells and DC calcium mobilization and chemotaxis to histamine.

          Conclusion

          Blockade of both H1R and H4R in the challenge phase had additive effects in preventing the intestinal consequences of peanut sensitization and challenge. These effects were mediated through limitation of mesenteric lymph node and intestinal DC accumulation and function. Identification of this histamine-H1R/H4R-DC-CD4 + T cell axis provides new insights into the development of peanut-induced intestinal allergic responses and for prevention and treatment of peanut allergy.

          Related collections

          Author and article information

          Journal
          7804028
          372
          Allergy
          Allergy
          Allergy
          0105-4538
          1398-9995
          8 April 2016
          3 August 2016
          November 2016
          01 November 2017
          : 71
          : 11
          : 1561-1574
          Affiliations
          Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO 80206
          Author notes
          Corresponding Author: Erwin W. Gelfand, MD, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, Ph: 303-398-1196, Fax: 303-270-2105, gelfande@ 123456njhealth.org
          Article
          PMC5052097 PMC5052097 5052097 nihpa775207
          10.1111/all.12904
          5052097
          27059534
          4465d647-ec76-4e2e-8737-439975674a8b
          History
          Categories
          Article

          H1R,CD4+ T cells,dendritic cells,peanut allergy,H4R
          H1R, CD4+ T cells, dendritic cells, peanut allergy, H4R

          Comments

          Comment on this article