Phenotype, function and clinical significance of innate lymphoid cells in immunoglobulin G4-related disease.

Objective 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, 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. RT-qPCR was performed to analyze the expression pattern of ILC2 associated genes between HCs and IgG4-RD patients. In addition, correlation analysis was performed in order to evaluate clinical significance of ILCs in IgG4-RD. Results The frequency of circulating pan ILCs in IgG4-RD patients was lower than in HCs. ILC2s was higher in IgG4-RD compared with HCs, whereas ILC1s was lower in IgG4-RD. sST2 and ST2L were increased in IgG4-RD than HC. Infiltration of ILC1s in submandibular glands of IgG4-RD was more prominent than ILC2s. Intracellular secretion of IL-9 was increased in ILC2s of IgG4-RD than in HCs. Circulating ILC2s correlated positively with Treg cells, the surface expression of CD154, PD-1 and CXCR5 in ILC2s correlated positively with CD19+B cells, serum IgG4 level 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.