The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets in neuromyelitis optica spectrum disorder

Abstract

B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are certain B cells that suppress immune responses by producing regulatory cytokines, such as IL-10. In this study, we investigated the presence of IL-10-producing Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples) were enrolled. All NMOSD patients have received one or more immunosuppressive drugs. The phenotype and frequency of B cell and T cell subsets in the peripheral blood were measured by flow cytometry. We defined Breg cells as IL-10-producing B (B10) cells, which are CD19(+)CD39(+)CD1d(+)IL-10(+). The potential relations were evaluated between specific lymphocyte subsets and AQP4-ab intensity measured by the cell-based indirect immunofluorescence assay. The frequency of B10 cells was higher in patients with NMOSD regardless of the disease status than that in HCs (attack samples; p = 0.009 and remission samples; p < 0.001, respectively). In addition, the frequency of IL-17(+) Treg cells among Treg cells was higher during remission than during an attack (uncorrected p = 0.032). Among the lymphocyte subsets, B10 cells alone showed a positive correlation with the intensity of AQP4-ab positivity (rho [rho] = 0.402 and p = 0.031). It was suggested that the suppressive subsets including B10 and IL-17(+) Treg cells might have important roles in controlling disease status in NMOSD. Further functional studies may help to elucidate the immunological role of B10 and IL-17(+) Treg cells in NMOSD.