Table_4_Allergen sensitization stratifies IL-31 production by memory T cells in atopic dermatitis patients.xlsx

BackgroundThe role of allergen sensitization in IL-31 production by T cells and specifically in the clinical context of atopic dermatitis (AD) has not been characterized.
MethodsThe response to house dust mite (HDM) in purified memory T cells cocultured with epidermal cells from AD patients (n=58) and control subjects (n=11) was evaluated. AD-associated cytokines from culture supernatants, plasma proteins and mRNA expression from cutaneous lesions were assessed and related with the clinical features of the patients.
ResultsHDM-induced IL-31 production by memory T cells defined two subsets of AD patients according to the presence or absence of IL-31 response. Patients in the IL-31 producing group showed a more inflammatory profile, and increased HDM-specific (sp) and total IgE levels compared to the IL-31 non-producing group. A correlation between IL-31 production and patient’s pruritus intensity, plasma CCL27 and periostin was detected. When the same patients were analyzed based on sp IgE and total IgE levels, an increased IL-31 in vitro response, as well as type 2 markers in plasma and cutaneous lesions, was found in patients with sp IgE levels > 100 kUA/L and total IgE levels > 1000 kU/L. The IL-31 response by memory T cells was restricted to the cutaneous lymphocyte-associated antigen (CLA)+ T-cell subset.
ConclusionIgE sensitization to HDM allows stratifying IL-31 production by memory T cells in AD patients and relating it to particular clinical phenotypes of the disease.

背景：变应原致敏在T细胞产生白介素31（IL-31）中的作用，尤其是在特应性皮炎（atopic dermatitis, AD）临床场景中的相关机制尚未被阐明。
方法：本研究评估了纯化记忆T细胞与AD患者（n=58）及健康对照受试者（n=11）的表皮细胞共培养后，对屋尘螨（house dust mite, HDM）的应答情况。同时检测了培养上清液中的AD相关细胞因子、血浆蛋白水平，以及皮肤皮损组织的mRNA表达水平，并将上述指标与患者的临床特征进行关联分析。
结果：基于记忆T细胞产生屋尘螨诱导的IL-31的应答情况，可将AD患者分为IL-31应答阳性与阴性两个亚群。与IL-31非产生组患者相比，IL-31产生组患者表现出更为显著的炎症表型，且屋尘螨特异性（specific, sp）IgE及总IgE水平均更高。研究还发现，IL-31的产生水平与患者瘙痒程度、血浆CCL27及骨膜蛋白（periostin）水平呈显著相关性。进一步根据sp IgE与总IgE水平对同一队列患者进行亚组分析后显示，sp IgE＞100 kUA/L且总IgE＞1000 kU/L的患者，其体外IL-31应答水平以及血浆与皮肤皮损中的2型炎症标志物水平均显著升高。此外，记忆T细胞的IL-31应答仅局限于皮肤淋巴细胞相关抗原（cutaneous lymphocyte-associated antigen, CLA）阳性的T细胞亚群。
结论：针对屋尘螨的IgE致敏可用于区分AD患者记忆T细胞的IL-31产生表型，并将其与该疾病的特定临床表型建立关联。