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Increased group 2 innate lymphoid cells in peripheral blood of adults with mastocytosis
Journal of Allergy and Clinical Immunology ( IF 14.2 ) Pub Date : 2020-10-20 , DOI: 10.1016/j.jaci.2020.09.037
Esmee K van der Ploeg 1 , Maud A W Hermans 2 , Vincent H J van der Velden 3 , Willem A Dik 3 , Paul L A van Daele 4 , Ralph Stadhouders 1
Affiliation  

Background

Systemic mastocytosis is a hematological disease in which aberrant mast cells accumulate because of gain-of-function mutations in the KIT receptor. Group 2 innate lymphoid cells (ILC2s) are effector cells of type 2 immune responses that also express KIT and colocalize with mast cells at barrier tissue sites. In mouse models, mast cell-ILC2 crosstalk can drive local inflammation. However, a possible role for ILC2s in the pathophysiology of mastocytosis remains unexplored.

Objective

We sought to characterize circulating ILC2s in a clinically diverse cohort of patients with mastocytosis.

Methods

We included 21 adults with systemic mastocytosis and 18 healthy controls. Peripheral blood ILC2 abundance and phenotype were analyzed by flow cytometry and correlated to clinical characteristics, including the presence of the D816V KIT mutation.

Results

ILC2 levels were significantly higher in D816V+ patients with mastocytosis compared with D816V− patients or healthy controls. We observed increased proportions of KIT+ ILC2s among patients with mastocytosis, regardless of D816V status. Patients with skin involvement and itch showed the highest levels of ILC2s, which was independent from atopy or serum tryptase levels. Allele-specific quantitative PCR showed that the vast majority of ILC2s did not carry the D816V mutation.

Conclusions

Our findings suggest a role for ILC2s and pathogenic ILC2-mast cell crosstalk in mastocytosis. We hypothesize that a high cutaneous D816V+ mast cell burden alters the skin microenvironment to induce chronic local ILC2 activation and their dissemination into the circulation. Activated ILC2s could contribute to skin symptoms by producing inflammatory mediators and by further augmenting mast cell mediator release.



中文翻译:

肥大细胞增多症成人外周血中第 2 组先天淋巴细胞增多

背景

系统性肥大细胞增多症是一种血液病,其中异常肥大细胞由于 KIT 受体的功能获得性突变而积聚。第 2 组先天淋巴细胞 (ILC2) 是 2 型免疫反应的效应细胞,它们也表达 KIT 并与屏障组织部位的肥大细胞共定位。在小鼠模型中,肥大细胞-ILC2 串扰可以驱动局部炎症。然而,ILC2s 在肥大细胞增多症的病理生理学中的可能作用仍有待探索。

客观的

我们试图在临床多样化的肥大细胞增多症患者队列中表征循环 ILC2。

方法

我们包括 21 名患有系统性肥大细胞增多症的成年人和 18 名健康对照。通过流式细胞术分析外周血 ILC2 丰度和表型,并与临床特征相关,包括 D816V KIT 突变的存在。

结果

与 D816V- 患者或健康对照相比,D816V +肥大细胞增多症患者的ILC2 水平显着更高。我们观察到肥大细胞增多症患者中 KIT + ILC2 的比例增加,无论 D816V 状态如何。皮肤受累和瘙痒的患者显示出最高水平的 ILC2,这与特应性或血清类胰蛋白酶水平无关。等位基因特异性定量 PCR 显示绝大多数 ILC2 不携带 D816V 突变。

结论

我们的研究结果表明 ILC2s 和致病性 ILC2-肥大细胞串扰在肥大细胞增多症中的作用。我们假设高皮肤 D816V +肥大细胞负荷会改变皮肤微环境,以诱导慢性局部 ILC2 激活及其扩散到循环中。激活的 ILC2 可通过产生炎症介质和进一步增加肥大细胞介质释放来导致皮肤症状。

更新日期:2020-10-20
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