Histamine-Releasing Factor Is a Novel Alarmin Induced by House Dust Mite Allergen, Cytokines, and Cell Death.
Histamine-Releasing Factor Is a Novel Alarmin Induced by House Dust Mite Allergen, Cytokines, and Cell Death.
复制标题
DOI：
10.4049/jimmunol.2200276
复制
发表时间：
2022-11-15
期刊：
影响因子：
--
通讯作者：
Kawakami T
中科院分区：
文献类型：
--
作者：
Kasakura K;Kawakami Y;Jacquet A;Kawakami T
组胺释放因子（HRF）是一种多功能蛋白，具有控制细胞存活和增殖的基本功能。HRF也在过敏反应中分泌，并促进ige介导的肥大细胞和嗜碱性粒细胞的活化。在这项研究中，我们研究了HRF分泌及其与气道炎症的相关性。HRF单体从BEAS-2B人支气管上皮细胞（HBECs）组成性分泌，并在培养过程中转化为低聚物。屋尘螨提取物（HDM）刺激可显著增加HRF分泌。参与哮喘发病机制的几种细胞因子对HRF分泌的影响中等，但显著增强hdm诱导的HRF分泌。hdm诱导的BEAS-2B细胞和正常HBECs的HRF分泌通过TLR2进行。与此一致的是，包括Der p2、Der p5、Der p13和Der p21在内的多个TLR2配体诱导HRF分泌。Der p10（原肌球蛋白）也促进HRF分泌。细胞死亡或与腺苷和ATP（细胞死亡时释放的化合物）孵育也能增强HRF的分泌。此外，经鼻给药重组HRF以高亲和力IgE受体（FcεRI）依赖的方式在hdm致敏小鼠中引起强烈的气道炎症。因此，我们得出结论，HRF是一种促进过敏性气道炎症的新型警报因子。
Histamine-releasing factor (HRF) is a multifunctional protein with fundamental intracellular functions controlling cell survival and proliferation. HRF is also secreted during allergic reactions and promotes IgE-mediated activation of mast cells and basophils. In this study, we investigated HRF secretion and its relevance to airway inflammation. HRF monomers were constitutively secreted from BEAS-2B human bronchial epithelial cells (HBECs), and converted to oligomers over the course of culture. Stimulation with house dust mite extract (HDM) increased HRF secretion substantially. Several cytokines involved in asthma pathogenesis showed moderate effects on HRF secretion, but dramatically enhanced HDM-induced HRF secretion. HDM-induced HRF secretion from BEAS-2B cells and normal HBECs proceeded via TLR2. Consistent with this, multiple TLR2 ligands including Der p 2, Der p 5, Der p 13, and Der p 21 induced HRF secretion. Der p 10 (tropomyosin) also promoted HRF secretion. Cell deaths or incubation with adenosine and ATP, compounds released upon cell death, also enhanced HRF secretion. Furthermore, intranasal administration of recombinant HRF elicited a robust airway inflammation in HDM-sensitized mice in a high-affinity IgE receptor (FcεRI)-dependent manner. Therefore, we conclude that HRF is a novel alarmin that promotes allergic airway inflammation.