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Intestinal mast cell-derived leukotrienes mediate the anaphylactic response to ingested antigens
摘要
Anaphylaxis is a life-threatening complication of food allergen exposure. Although mechanisms governing anaphylaxis after intravenous injection are defined in mice, these models neglect mucosal exposure that accompanies ingestion. We investigated the role of mast cells within the intestine of mice and found that oral anaphylaxis required immunoglobulin E-Fcε receptor 1 (IgE-FcεR1) signaling. Intestinal mast cells were a heterogeneous population, shaped by epithelial cues. Compared with connective tissue mast cells found throughout the body, intestinal mast cells largely resided in the epithelium, displayed divergent transcriptomes and effector functions, and had a diminished ability to generate histamine, but they enhanced leukotriene synthesis. Mice genetically deficient in cysteinyl leukotriene synthesis, or those treated with the arachidonate 5-lipoxygenase (aLOX5) antagonist zileuton, were protected from oral antigen-induced responses, whereas those elicited by intravenous injection were unaltered.
实验方法
产品清单
| 名称 | 品牌 | 货号 |
|---|---|---|
| Gammacell 40 137Cs γ辐射源 | -- | -- |
| Amicon Ultra 4 3K过滤装置 | Sigma | -- |
| SpectraMax M5酶标仪 | Molecular Devices | -- |
| BD LSRII分析仪 | BD | -- |
| BD Symphony分析仪 | BD | -- |
| FlowJo软件 | -- | -- |
| FACS Aria细胞分选仪 | -- | -- |
| CFX384实时系统 | Bio-Rad | -- |
| Illumina NextSeq 500测序仪 | Illumina | NextSeq 500 |
| NovaSeq 6000测序仪 | -- | NovaSeq 6000 |
| Chromium GEM-X Single Cell 3’ v4试剂盒 | 10X Genomics | -- |
| Thermalert TH5体温计 | -- | TH5 |
| 血细胞比容管 | BD Clay Adams Sure Prep | -- |
| ELISA级板 | VWR | 490012–252 |
| RNeasy Micro试剂盒 | Qiagen | -- |
| RNeasy Plus Micro试剂盒 | Qiagen | -- |
| BD Cytofix/Cytoperm试剂盒 | BD | -- |
| AF647标记试剂盒 | Invitrogen | -- |