Involvement of ICOS and IL-10 Positive Regulatory T Cells in the Development of IgG4-Related Autoimmune Pancreatitis

Abstract

Objectives: IgG4-related autoimmune pancreatitis (AIP) is a new clinical entity of pancreatic disorder. There are immunologic and histological abnormalities, including increased serum IgG4 levels and the infiltration of lymphocytes and IgG4-positive plasmacytes. However, the role of IgG4 is unclear. Recently, regulatory T cells (Tregs) were reported to contribute to the development of various autoimmune diseases as well as in B cell shifting to IgG4producing plasmacytes. For this report, we studied regulatory T cells in the pancreas by immunohistochemistory and ICOS+ Tregs and IL-10 producing cells in the peripheral blood lymphocytes by flowcytometry. Methods: We recruited 44 patients with IgG4-related AIP. For comparison, we recruited 37 patients with other pancreatic diseases and 27 healthy subjects as controls. We studied infiltrating cells in the pancreas by immunohistochemistry, and analyzed ICOS+ Tregs and IL-10+ Tregs in the peripheral blood by flow cytometry. Results: The ratio of Foxp3-positive cells to infiltrated mononuclear cells (Foxp3/Mono) in AIP patients (0.091 ± 0.023) was significantly higher than in patients with alcoholic chronic pancreatitis (0.012 ± 0.003; p<0.05). In AIP, Foxp3/Mono and IgG4/Mono were positively correlated (p<0.05; R =0.91). ICOS+ Tregs (%ICOS-positive Tregs of total Tregs) were significantly higher in AIP patients (3.45% ± 1.58%) than in the patients with other pancreatic diseases (alcoholic chronic pancreatitis; 1.71% ± 0.98%, idiopathic chronic pancreatitis; 1.80% ± 0.86%) and the healthy control group (1.57% ± 0.69%, p<0.05). IL-10+ Tregs were significantly higher in AIP patients than in the healthy control group. Conclusions: Increased quantities of ICOS+ Tregs may influence IgG4 production in IgG4-related AIP.