Objectives The innate immune system participates in immunoglobulin G4–related disease (IgG4-RD). While the role of innate lymphoid cells (ILCs) in IgG4-RD remains to be elucidated, we aimed to evaluate the phenotype, function and clinical significance of ILCs in IgG4-RD patients. Methods Sixty-seven untreated IgG4-RD patients and 44 age- and sex-matched healthy controls (HCs) were enrolled. Circulating and tissue infiltration of ILCs were detected by flow cytometry. Serum suppression of tumorigenicity 2 (sST2) was detected by ELISA and membrane-bound ST2 (ST2L) was detected by flow cytometry. Tissue infiltration of IL-33 was measured by immunohistochemistry staining. Real-time quantitative PCR was performed to analyse the expression pattern of ILC2-associated genes between HCs and IgG4-RD patients. In addition, correlation analysis was performed in order to evaluate the clinical significance of ILCs in IgG4-RD. Results The frequency of circulating pan ILCs in IgG4-RD patients was lower than in HCs. ILC2s were higher in IgG4-RD compared with HCs, whereas ILC1s were lower in IgG4-RD. sST2 and ST2L were higher in IgG4-RD than in HCs. Infiltration of ILC1s in the submandibular glands of IgG4-RD patients was more prominent than ILC2s. Intracellular secretion of IL-9 was increased in ILC2s of IgG4-RD patients than in HCs. Circulating ILC2s correlated positively with Treg cells and the surface expression of CD154, PD-1 and CXCR5 in ILC2s correlated positively with CD19+ B cells, serum IgG4 levels and serum IgE, respectively. Conclusion ILCs and their subsets were significantly altered in IgG4-RD. We demonstrated the dysfunction of ILC2s in IgG4-RD by phenotype, correlation analysis and function investigation, revealing ILC2s participated in the pathogenesis of IgG4-RD.

中文翻译：

---

先天淋巴细胞在免疫球蛋白 G4 相关疾病中的表型、功能和临床意义

目的 先天免疫系统参与免疫球蛋白 G4 相关疾病 (IgG4-RD)。虽然先天淋巴细胞 (ILC) 在 IgG4-RD 中的作用仍有待阐明，但我们旨在评估 ILC 在 IgG4-RD 患者中的表型、功能和临床意义。方法 67 名未经治疗的 IgG4-RD 患者和 44 名年龄和性别匹配的健康对照 (HC) 被纳入研究。通过流式细胞术检测ILC的循环和组织浸润。ELISA检测血清抑制致瘤性2（sST2），流式细胞仪检测膜结合ST2（ST2L）。通过免疫组织化学染色测量IL-33的组织浸润。进行实时定量 PCR 以分析 HCs 和 IgG4-RD 患者之间 ILC2 相关基因的表达模式。此外，进行相关性分析以评估 ILC 在 IgG4-RD 中的临床意义。结果 IgG4-RD 患者循环泛 ILCs 的频率低于 HCs。与 HCs 相比，IgG4-RD 中的 ILC2 更高，而 IgG4-RD 中的 ILC1 更低。IgG4-RD 中的 sST2 和 ST2L 高于 HC。IgG4-RD 患者下颌下腺 ILC1 的浸润比 ILC2 更显着。与 HCs 相比，IgG4-RD 患者的 ILC2 中 IL-9 的细胞内分泌增加。循环ILC2s与Treg细胞呈正相关，ILC2s中CD154、PD-1和CXCR5的表面表达分别与CD19+ B细胞、血清IgG4水平和血清IgE呈正相关。结论 ILC 及其亚群在 IgG4-RD 中发生了显着改变。我们通过表型证明了 IgG4-RD 中 ILC2 的功能障碍，