Department of Molecular Pneumology, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
Translational Genomics Core, Partners Biobank, Partners HealthCare, Personalized Medicine, Cambridge, MA, USA.
Clin Exp Immunol. 2018 Aug;193(2):207-220. doi: 10.1111/cei.13135. Epub 2018 May 31.
Paediatric asthma exacerbations are often caused by rhinovirus (RV). Moreover, 25(OH)-vitamin D3 (VitD3) deficiency during infancy was found associated with asthma. Here, we investigated the innate immune responses to RV and their possible modulation by 25(OH)-VitD3 serum levels in a preschool cohort of children with and without asthma. The innate lymphoid cell type 2 (ILC2)-associated marker, ST2, was found up-regulated in the blood cells of asthmatic children with low serum levels of 25(OH)-VitD3 in the absence of RV in their airways. Furthermore, in blood cells from control and asthmatic children with RV in their airways, soluble (s) ST2 (sST2) protein was found reduced. Asthmatic children with low 25(OH)-VitD3 in serum and with RV in vivo in their airways at the time of the analysis had the lowest sST2 protein levels in the peripheral blood compared to control children without RV and high levels of 25(OH)-VitD3. Amphiregulin (AREG), another ILC2-associated marker, was found induced in the control children with RV in their airways and low serum levels of 25(OH)-VitD3. In conclusion, the anti-inflammatory soluble form of ST2, also known as sST2, in serum correlated directly with interleukin (IL)-33 in the airways of asthmatic children. Furthermore, RV colonization in the airways and low serum levels of 25(OH)-VitD3 were found to be associated with down-regulation of sST2 in serum in paediatric asthma. These data indicate a counter-regulatory role of 25(OH)-VitD3 on RV-induced down-regulation of serum sST2 in paediatric asthma, which is relevant for the therapy of this disease.
儿童哮喘发作通常由鼻病毒（RV）引起。此外，婴儿期 25（OH）-维生素 D3（VitD3）缺乏与哮喘有关。在这里，我们研究了先天免疫对 RV 的反应及其对哮喘和非哮喘学龄前儿童血清 25（OH）-VitD3 水平的可能调节作用。在气道中没有 RV 的情况下，哮喘患儿的血细胞中发现先天淋巴细胞 2 型（ILC2）相关标志物 ST2 上调，并且在气道中存在 RV 的对照组和哮喘患儿的血细胞中发现可溶性（s）ST2（sST2）蛋白减少。在分析时血清中 25（OH）-VitD3 水平低且体内存在 RV 的哮喘患儿与对照组相比，其外周血中 sST2 蛋白水平最低，且无 RV 且 25（OH）-VitD3 水平高的儿童。另一种 ILC2 相关标志物 Amphiregulin（AREG）也被发现存在于气道中存在 RV 且血清中 25（OH）-VitD3 水平低的对照组中。总之，血清中抗炎性的可溶性 ST2 形式，也称为 sST2，与哮喘患儿气道中的白细胞介素（IL）-33直接相关。此外，气道中 RV 定植和血清中 25（OH）-VitD3 水平低与儿科哮喘患者血清中 sST2 的下调有关。这些数据表明 25（OH）-VitD3 对 RV 诱导的血清 sST2 下调具有拮抗作用，这与该疾病的治疗有关。
