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

Abstract

Objectives: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords:

• Allergy
• eosinophils
• IgG4-related disease
• interleukin-5
• ST2

Conflict of interest

None.

Additional information

Funding

This work was supported by the Research on Measures for Intractable Diseases Project Matching Fund Subsidy from the Ministry of Health, Labour, and Welfare, Japan, and the Japan Agency for Medical Research and Development; Grant-in-Aid for Scientific Research, Japan Society for the Promotion of Science; the Suhara Memorial Foundation, and the Takeda Science Foundation.