Dysfunction of CD24+CD38+ B cells in patients with Hashimoto’s thyroiditis is associated with a lack of interleukin 10

Abstract

Autoimmune thyroid disease (AITD) is characterized by immune attacks on the person’s own thyroid. Hashimoto’s thyroiditis (HT) is a subtype of AITD and is a common cause of hypothyroidism and related symptoms. Regulatory B (Breg) cells can express interleukin 10 (IL-10) and have recently emerged as a critical participant in suppression pathogenic inflammation and promoting peripheral tolerance. The role of Breg cells in HT is not yet clear. In this study, we first examined the IL-10 production by B cells in healthy controls and HT patients, and found that the healthy control B cells demonstrated significantly higher IL-10 expression than HT B cells after CpG stimulation. In both groups, the IL-10-producing B cells were highly enriched in the CD24+CD38+ compartment. However, compared to healthy controls, HT patients presented higher levels of circulating CD24+CD38+ B cells, but lower percentage of IL-10+ cells in the CD24+CD38+ B cell compartment. In healthy controls, we performed coculture experiments of T cells with autologous total B cells, CD24+CD38+ B cells, and non-CD24+CD38+ B cells, and found significantly lower T cell proliferation as well as tumor necrosis factor (TNF) and interferon gamma (IFN-γ) production in cell cultures containing CD24+CD38+ B cells. In contrast, the HT CD24+CD38+ B cells demonstrated reduced capacity in suppressing T cell proliferation and did not suppress TNF and IFN-γ production. This lack of inhibitory activity in HT CD24+CD38+ B cells was related to a lack of IL-10, since addition of exogenous IL-10 in CD24+CD38+ B cell-T cell coculture significantly suppressed the proliferation of T cells and reduced proinflammatory cytokine secretion. Together, our study identified an upregulation of CD24+CD38+ B cells but a downregulation in their regulatory activity in HT patients.