An inhibitory immunoreceptor, Allergin-1, suppresses FITC-induced type 2 contact hypersensitivity
An inhibitory immunoreceptor, Allergin-1, suppresses FITC-induced type 2 contact hypersensitivity
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抑制性免疫受体 Allergin-1 可抑制 FITC 诱导的 2 型接触超敏反应
DOI：
10.1016/j.bbrc.2021.09.048
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Shibuya A
中科院分区：
文献类型：
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作者：
Almeida M;Shibagaki S;Tahara-Hanaoka S;Shibayama S;Shibuya A
虽然变态反应性接触性皮炎(ACD)是皮肤中最常见的T细胞介导的针对过敏原的炎症反应，但ACD的发病机制仍不完全清楚。在ACD的致敏阶段，含半抗原的真皮树突状细胞(DC)在将抗原运送到淋巴结(LNS)中起着关键作用，在LNS中它们将抗原呈递给幼稚的T细胞。在此，我们报道了Allergin-1，一种位于细胞质区域的含有免疫受体酪氨酸抑制基序(ITIM)的抑制性免疫受体，在真皮DC上高度表达。Allergin-1基因缺陷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(CHS)，如耳朵肿胀和皮肤嗜酸性粒细胞增多症。与野生型小鼠相比，Allergin-1基因缺陷小鼠在引流的LNS中也显示出更多的CD4+T细胞和携带FITC的DC，以及更多的2型细胞因子，包括IL-5，IL-10和IL-13的表达。与此形成鲜明对比的是，Allergin-1基因缺陷小鼠表现出与2，4-二硝基氟苯(DNFB)诱导的1型CHS水平相当的水平。这些结果表明，真皮DC上的Allergin-1在CHS致敏阶段抑制2型免疫反应，但不抑制1型免疫反应。
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.