Erciyes University School of Medicine, Department of Medical Biology, Kayseri, Turkey; Erciyes University, Betul-Ziya Eren Genome and Stem Cell Center, Kayseri, Turkey.
Ankara University School of Medicine, Department of Pediatric Allergy and Immunology, Ankara, Turkey.
Clin Immunol. 2023 Aug;253:109691. doi: 10.1016/j.clim.2023.109691. Epub 2023 Jul 9.
In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4 T cells were decreased despite the elevated absolute counts of CD4 cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4 T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis. Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.
在 15 名土耳其 LAD-1 患者和对照组中，我们评估了致病性 ITGB2 突变对 Th17/Treg 分化和功能以及固有淋巴细胞 (ILC) 亚群的影响。尽管 LAD-1 患者的 CD4 细胞绝对计数升高，但外周血 Treg 细胞的百分比和体外从幼稚 CD4 T 细胞分化而来的诱导性 Treg 减少。LAD-1 患者的血清 IL-23 水平升高。在用 curdlan 刺激后，LAD-1 患者来源的 PBMC 产生更多的 IL-17A。此外，从总或幼稚 CD4 T 细胞扩增的 CD18 缺陷性 Th17 细胞的百分比更高。LAD-1 患者的血液 ILC3 亚群明显升高。最后，LAD-1 PBMC 在 Trans-well 迁移和增殖方面存在缺陷，并且对细胞凋亡的抵抗力更强。LAD-1 患者外周血中 CD18 缺陷性幼稚 T 细胞中 Treg 的从头生成缺陷以及 Th17 和 ILC3 的升高表明存在 3 型免疫偏倚，可能导致 LAD-1 相关的自身免疫症状。
