The function of IL-33/ST2 signaling axis in treg cells activating fibrosis in IgG4-related disease

Abstract

Objects: To explore whether IL-33/ST2 signaling axis can activate Treg cells in promoting tissue fibrosis in IgG4-related disease.

Methods: Peripheral blood from patients diagnosed as IgG4-related disease and healthy volunteers matched with age and sex from September 2019 to December 2020 in Sun Yat-sen Memorial Hospital was collected and disposed to separate the peripheral blood mononuclear cells and serum. The concentration of serum IL-33, IL-13 and ST2 was measured using ELISA kits. And the ratio of Treg cells was measured with flow cytometry. Patients diagnosed as type1 autoimmune pancreatitis from September 2019 to December 2020 in Sun Yat-sen Memorial Hospital were enrolled in this study. Patients diagnosed as pancreatic cancer and chronic pancreatitis were enrolled as controls. Pathological sections of these patients were collected and treated with Immunohistochemical staining and Masson trichrome staining in order to observe the expression of FoxP3, IL-33, IL-13 and ST2 as well as the grade of tissue fibrosis.

Results: We found that no matter in blood circulation or at the affected sites in IgG4-related disease, the expression of IL-33, IL-13 and ST2 was up regulated and Treg cells expanded. In type1 autoimmune pancreatitis, the degree of fibrosis was positively correlated to IL-33, IL-13, ST2 and FoxP3. Moreover, IL-33, IL-13, ST2 and Treg cells affected each other both in blood and in pancreas.

Conclusions: IL-33/ST2 may affect the expanding of Treg and the secretion of IL-13 in the fibrosis process in IgG4-RD.

Keywords: Cytokines; IgG4-related disease; ST2 receptor; Tissue fibrosis; Treg cells.