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An inhibitory immunoreceptor, Allergin-1, suppresses FITC-induced type 2 contact hypersensitivity
Biochemical and Biophysical Research Communications ( IF 2.5 ) Pub Date : 2021-09-23 , DOI: 10.1016/j.bbrc.2021.09.048
Mariana Silva Almeida 1 , Shohei Shibagaki 2 , Satoko Tahara-Hanaoka 3 , Shiro Shibayama 4 , Akira Shibuya 3
Affiliation  

Although allergic contact dermatitis (ACD) is the most common T cell-mediated inflammatory responses against an allergen in the skin, the pathogenesis of ACD remains incompletely understood. In the sensitization phase in ACD, hapten-bearing dermal dendritic cells (DCs) play a pivotal role in the transport of an antigen to the lymph nodes (LNs), where they present the antigen to naïve T cells. Here we report that Allergin-1, an inhibitory immunoreceptor containing immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic region, is highly expressed on dermal DCs. Mice deficient in Allergin-1 exhibited exacerbated fluorescein isothiocyanate (FITC)-induced type 2 contact hypersensitivity (CHS) such as ear swelling and skin eosinophilia. Allergin-1-deficient mice also showed larger numbers of CD4+ T cells and FITC-bearing DCs and greater expressions of type 2 cytokines, including IL-5, IL-10 and IL-13, in the draining LNs than did wild type mice. In sharp contrast, Allergin-1-deficient mice showed comparable level of type 1 CHS induced by 2,4-dinitrofluorobenzene (DNFB). These results suggest that Allergin-1 on dermal DC inhibits type 2, but not type 1, immune responses in the sensitization phase of CHS.



中文翻译:

抑制性免疫受体 Allergin-1 抑制 FITC 诱导的 2 型接触过敏症

尽管过敏性接触性皮炎 (ACD) 是最常见的 T 细胞介导的针对皮肤过敏原的炎症反应,但 ACD 的发病机制仍未完全了解。在 ACD 的致敏阶段,携带半抗原的真皮树突细胞 (DC) 在将抗原转运至淋巴结 (LN) 中发挥关键作用,在淋巴结 (LN) 中,它们将抗原呈递给幼稚 T 细胞。在这里我们报告 Allergin-1 是一种抑制性免疫受体,在细胞质区域中含有基于免疫受体酪氨酸的抑制基序 (ITIM),在真皮 DC 上高度表达。缺乏 Allergin-1 的小鼠表现出加重的异硫氰酸荧光素 (FITC) 诱导的 2 型接触过敏症 (CHS),例如耳肿胀和皮肤嗜酸性粒细胞增多症。Allergin-1 缺陷小鼠也表现出更多的 CD4 +T 细胞和带有 FITC 的 DC 以及 2 型细胞因子(包括 IL-5、IL-10 和 IL-13)在引流 LN 中的表达比野生型小鼠更高。与此形成鲜明对比的是,Allergin-1 缺陷小鼠表现出相当水平的 2,4-二硝基氟苯 (DNFB) 诱导的 1 型 CHS。这些结果表明,真皮 DC 上的 Allergin-1 抑制 CHS 致敏阶段的 2 型而非 1 型免疫反应。

更新日期:2021-09-30
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