The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses
The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses
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DOI：
10.1111/all.13129
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发表时间：
2017-07-01
期刊：
影响因子：
12.4
通讯作者：
Poulsen, L. K.
中科院分区：
文献类型：
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作者：
Blom, L. H.;Martel, B. C.;Poulsen, L. K.
背景：过敏性疾病的病理涉及 2 型免疫细胞，如 Th2、ILC2 和嗜碱性粒细胞通过产生 IL-4、IL-5 和 IL-13 发挥作用。然而，2 型免疫细胞上特异性表达的表面受体的记录较少。本研究的目的是确定与 2 型炎症相关的表面标志物。方法：在存在或不存在 IL-4 的情况下短期激活初始人类 CD4(+) T 细胞，并分析 > 300 种细胞表面蛋白的表达。用花生提取物刺激（14-16小时）花生过敏（PA）和非过敏受试者的离体分离的外周血单核细胞（PBMC）以检测花生特异性CD4（+）CD154（+）T细胞。从健康对照者以及患有外源性或内源性特应性皮炎 (AD) 和银屑病的患者中获取活组织检查以进行转录组分析。结果：对超过 300 种表面蛋白的表达分析能够识别 IL-4 上调的表面蛋白，例如 CD90、CD108、CD109 和 CD200R (CD200R1)。对体外分化的 Th0、Th1 和 Th2 培养物的进一步分析发现，CD200R 在 Th2 细胞上表达上调。从离体分离的 PBMC 中，我们发现 Th2 和 ILC2 细胞以及嗜碱性粒细胞上 CD200R 高表达。在 PA 受试者中，花生特异性 Th2 (CD154(+) CRTh2(+)) 细胞比非过敏原特异性 Th2 (CD154(-) CRTh2(+)) 细胞表达更多的 CD200R。此外，CD161和CD200R的共染色鉴定了花生特异性的高度分化的IL-4(+) IL-5(+) Th2细胞。最后，转录组分析显示，与健康皮肤相比，具有外在 AD 表型的受试者的病变皮肤中 CD200R 上调。结论：这些结果表明 CD200R 表达与 Th2 病理学密切相关；然而，其机制尚不清楚。
Background: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation.Methods: Naive human CD4(+) T cells were short-term activated in the presence or absence of IL-4 and analyzed for expression of > 300 cell-surface proteins. Ex vivo-isolated peripheral blood mononuclear cells (PBMCs) from peanut-allergic (PA) and nonallergic subjects were stimulated (14-16 h) with peanut extract to detect peanut-specific CD4(+) CD154(+) T cells. Biopsies were obtained for transcriptomic analysis from healthy controls and patients with extrinsic or intrinsic atopic dermatitis (AD) and psoriasis.Results: Expression analysis of > 300 surface proteins enabled identification of IL-4-upregulated surface proteins, such as CD90, CD108, CD109, and CD200R (CD200R1). Additional analysis of in vitro-differentiated Th0, Th1, and Th2 cultures identified CD200R as upregulated on Th2 cells. From ex vivo-isolated PBMCs, we found high expression of CD200R on Th2 and ILC2 cells and basophils. In PA subjects, the peanut-specific Th2 (CD154(+) CRTh2(+)) cells expressed more CD200R than the non-allergen-specific Th2 (CD154(-) CRTh2(+)) cells. Moreover, costaining of CD161 and CD200R identified peanut-specific highly differentiated IL-4(+) IL-5(+) Th2 cells. Finally, transcriptomic analysis revealed upregulation of CD200R in lesional skin from subjects with an extrinsic AD phenotype compared to healthy skin.Conclusion: These results indicate that CD200R expression strongly correlates with Th2 pathology; though, the mechanism is as yet elusive.