Interleukin 5-producing ST2⁺ memory Th2 cells in IgG4-related dacryoadenitis and sialadenitis

<b>Objectives:</b> Immunoglobulin (Ig) G4-related disease (IgG4-RD) is often complicated by allergic disorders. This study was conducted to investigate the mechanism of type 2 helper T-inflammation (Th2-inflammation) in IgG4-related dacryoadenitis and sialadenitis (IgG4-DS). <b>Methods:</b> We separated and analyzed the proportion of growth stimulation expressed gene 2 (ST2)⁺ memory Th2 cells among the peripheral blood mononuclear cells by flow cytometry in cases with IgG4-DS and healthy individuals. Finally, we identified the role of ST2⁺ memory Th2 cells in the involved tissues. <b>Results:</b> The proportion of circulating ST2⁺ memory Th2 cells was much higher in the patients with IgG4-DS than in the healthy controls. Abundant infiltration of ST2⁺ memory Th2 cells was detected in the involved salivary glands and lymph nodes, and these cells produced interleukin-5. <b>Conclusion:</b> We demonstrated that there is an increase of interleukin-5 producing ST2⁺ memory Th2 cells in the involved tissues in IgG4-DS. This subset of cells is considered to be an important player in inducing the inflammatory Th2 environment characteristic of IgG4-DS.