Key Points Allergin-1 inhibits HDM-induced Syk activation via SHP-1 in CD11b+ DC. Allergin-1 suppresses Th2 response by inhibiting Syk-mediated PGE2 production in DC. Visual Abstract House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b+ dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b+ DC activation remains incompletely understood. In this study, we demonstrate that mice deficient in an inhibitory immunoreceptor, Allergin-1, showed exacerbated HDM-induced airway eosinophilia and serum IgE elevation. By using bone marrow–chimeric mice that were sensitized with adoptively transferred HDM-stimulated wild-type or Allergin-1–deficient CD11b+ bone marrow–derived cultured DCs (BMDCs), followed by challenge with HDM, we show that Allergin-1 on the BMDCs suppressed HDM-induced allergic airway inflammation. We also show that Allergin-1 suppressed HDM-induced PGE2 production from CD11b+ BMDCs by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in regulation of HDM-induced allergic airway inflammation.

中文翻译：

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Allergin-1 免疫受体抑制屋尘螨引起的过敏性气道炎症

关键点 Allergin-1 通过 CD11b+ DC 中的 SHP-1 抑制 HDM 诱导的 Syk 激活。Allergin-1 通过抑制 DC 中 Syk 介导的 PGE2 产生来抑制 Th2 反应。视觉摘要 屋尘螨 (HDM) 过敏原是以 Th2 反应为特征的过敏性哮喘的主要原因。肺驻留 CD11b+ 树突状细胞 (DC) 在 HDM 诱导的过敏性哮喘的 Th2 细胞发育中起关键作用。然而，HDM 诱导的 CD11b+ DC 激活的调节机制仍未完全了解。在这项研究中，我们证明了缺乏抑制性免疫受体 Allergin-1 的小鼠表现出加重的 HDM 诱导的气道嗜酸性粒细胞增多症和血清 IgE 升高。通过使用被过继转移的 HDM 刺激的野生型或过敏原-1 缺陷的 CD11b+ 骨髓来源的培养 DC（BMDC）致敏的骨髓嵌合小鼠，随后用 HDM 进行挑战，我们表明 BMDC 上的 Allergin-1 抑制了 HDM 诱导的过敏性气道炎症。我们还表明，Allergin-1 通过募集 SHP-1 抑制 Syk 酪氨酸激酶激活，从而抑制 HDM 诱导的 CD11b+ BMDC 产生的 PGE2，随后导致 Th2 反应的负调节。这些结果表明 Allergin-1 在调节 HDM 诱导的过敏性气道炎症中起重要作用。