Low frequency of IL-10-producing B cells and high density of ILC2s contribute to the pathological process in Graves’ disease, which may be related to elevated-TRAb levels

Abstract

IL-10-producing B Cells (B10) is a functionally defined regulatory B-cell subset. It plays an important role in the control of inflammation and autoimmune diseases, although it is present at low numbers in peripheral blood. Graves’ disease is an autoimmune disease characterized by the production of autoantibodies such as TRAb. ILC2s maintains Th2 polarization state by producing type-II cytokines. It is not clear whether the level of autoantibody is related to ILC2s and B10 cells in Graves’ disease. In this study, we analyzed the frequencies of B10, Treg cells and ILC2s, as well as the expression of related cytokines in peripheral blood from patients with Graves' disease and evaluated the correlation between B10 cell numbers and autoantibodies level. Our data showed that the frequency of B10 or Treg cells was significantly decreased in peripheral blood mononuclear cells from Graves' disease patients, while the percentage of ILC2s cells was increased; the levels of cytokine IL-5, IL-13 and related transcription factor RORα were up-regulated. Autoantibodies analysis also showed that high level of TRAb was accompanied by low rates of B10 cells in patients, there was a negative correlation trend. In addition, the analytical data from mouse disease models also showed similar results. It indicates that B10 cells may affect the production of TRAb by negative regulation of Th2 cells, while ILC2s can promote the production of autoantibodies such as TRAb by maintaining the dominant response state of Th2 cells.

Keywords:

• ILC2s
• B10 cells
• autoantibodies
• Graves’ disease

Acknowledgements

The skilled technical assistance of Huijian Yang, Miao Chen and Jianguo Chen are gratefully acknowledged. The authors also acknowledge Yingzhao Liu, Caixia Sun and Suoying Wang for support on sample collection.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China (81771756), Key University Science Research Project of Jiangsu Province (grant no. 16KJA320005), Social development project of Jiangsu Province (grant no. BE2016716) and the Postdoctoral Foundation of Jiangsu Province (grant no. 1601002 C).