Combined blockade of the histamine H1 and H4 receptor suppresses peanut-induced intestinal anaphylaxis by regulating dendritic cell function
M. Wang
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorJ. Han
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorJ. Domenico
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorY. S. Shin
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorY. Jia
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorCorresponding Author
E. W. Gelfand
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Correspondence
Erwin W. Gelfand, MD, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
Tel.: 303-398-1196
Fax: 303-270-2105
E-mail: [email protected]
Search for more papers by this authorM. Wang
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorJ. Han
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorJ. Domenico
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorY. S. Shin
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorY. Jia
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Search for more papers by this authorCorresponding Author
E. W. Gelfand
Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO, USA
Correspondence
Erwin W. Gelfand, MD, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
Tel.: 303-398-1196
Fax: 303-270-2105
E-mail: [email protected]
Search for more papers by this authorAbstract
Background
Signaling through histamine receptors on dendritic cells (DCs) may be involved in the effector phase of peanut-induced intestinal anaphylaxis.
Objectives
The objective of this study was 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 with 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 nonsensitized WT mice. Symptoms, intestinal inflammation, and 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 the 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 the 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 the 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.
Supporting Information
| Filename | Description |
|---|---|
| all12904-sup-0001-FigE1.tiffTIFF image, 1.5 MB | Figure S1. Decreased mast cell infiltration in the jejunum of PE sensitized and challenged mice treated with H1R and H4R antagonists. |
| all12904-sup-0002-FigE2.tiffTIFF image, 1.5 MB | Figure S2. Decreased numbers of eosinophils in the jejunum of PE sensitized and challenged mice treated with H1R and H4R antagonists. |
| all12904-sup-0003-FigE3.tiffTIFF image, 1.5 MB | Figure S3. Decreased numbers of goblet cells in the jejunum of PE sensitized and challenged mice treated with H1R and H4R antagonists. |
| all12904-sup-0004-FigE4.tiffTIFF image, 1.5 MB | Figure S4. Treatment with H1R and H4R antagonists had no effect on serum peanut-specific immunoglobulin levels in peanut sensitized and challenged mice. |
| all12904-sup-0005-FigE5.tiffTIFF image, 1.5 MB | Figure S5. Cell viability in DCs treated with histamine and loratadine (10 µM) and/or JNJ7777120 (10 µM) in vitro cultures (A). Cell viability in T cells and treated DCs co-culture in vitro (B). |
| all12904-sup-0006-FigE6.tiffTIFF image, 1.5 MB | Figure S6. Decreased mast cell infiltration in the jejunum of recipients of PE-primed DCs and PE challenge treated with H1R and H4R antagonists. |
| all12904-sup-0007-FigE7.tiffTIFF image, 1.5 MB | Figure S7. Decreased numbers of eosinophils in the jejunum of recipients of PE-primed DCs and PE challenge treated with H1R and H4R antagonists. |
| all12904-sup-0008-FigE8.tiffTIFF image, 1.5 MB | Figure S8. Decreased numbers of goblet cells in the jejunum of recipients of PE-primed DCs and PE challenge treated with H1R and H4R antagonists. |
| all12904-sup-0009-FigE9.tiffTIFF image, 1.5 MB | Figure S9. Treatment with H1R and H4R antagonists had no effect on serum immunoglobulin production in recipients of PE-primed DCs and PE challenge. |
| all12904-sup-0010-FigE10.tiffTIFF image, 1.5 MB | Figure S10. Effects of H1R and H4R antagonist administration on cytokine and lineage-specific transcription factor expression following DC transfer and allergen challenge. |
| all12904-sup-0011-SupInfo.docWord document, 33 KB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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