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Interleukin 10 (IL-10)-producing regulatory B-cells (Bregs) suppress inflammatory responses that mediate autoimmune diseases. However, it is unknown whether Bregs derive from a pre-existing dedicated B-cell lineage or if any B-cell can differentiate into Bregs in response to BCR or TLR activation. GL7 + B-cells are antigen-experienced differentiated B-cells while GL7 −/lo are at an early stage of B-cell differentiation. While both GL7 −/lo and GL7 + B cells can produce IL-10, differentiation of GL7 − B-cells into Bregs does not require CD19- or Bcl6-induced signals, suggesting that BCR-induced proliferation or Ig class-switching is not necessary for generation of Breg cells. Of particular importance, we show that GL7 − Breg cells are dramatically expanded in lupus-like mice and GL7 − Bregs suppressed inflammatory responses in lupus-like mice by inducing expansion of Foxp3 + Treg cells. Taken together, these results suggest that pre-existing GL7 − IL-10 + cells are expanded during inflammation, differentiate into GL7 + Bregs and contribute to immune-regulation in lupus-like mice. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that exosomes from dendritic cells (DCs) secreting TGF-β1 (sTGF-β1-EXOs) delay the development of murine inflammatory bowel disease (IBD). In this study, we isolated exosomes from DCs expressing membrane-associated TGF-β1 (mTGF-β1-EXOs) and found mTGF-β1-EXOs had more potent immunosuppressive activity than sTGF-β1-EXOs in vitro. Treatment of mice with mTGF-β1-EXOs inhibited the development and progression of myelin oligodendrocyte glycoprotein (MOG) peptide-induced EAE even after disease onset. Treatment of mice with mTGF-β1-EXOs also impaired Ag-specific Th1 and IL-17 responses, but promoted IL-10 responses ex vivo. Treatment with mTGF-β1-EXOs decreased the frequency of Th17 cells in EAE mice, which might be associated with the down-regulation of the p38, ERK, Stat3, and NF-κB activation and IL-6 expression in DCs. Treatment with mTGF-β1-EXOs maintained the regulatory capacity of Treg cells, and adoptive transfer of CD4+Foxp3+ Treg cells from mTGF-β1-EXO-treated EAE mice dramatically prevented the development of EAE in the recipients. Moreover, treatment with mTGF-β1-EXOs from C57BL/6 mice effectively prevented and inhibited proteolipid protein (PLP) peptide-induced EAE in BALB/c mice. These results indicate that mTGF-β1-EXOs possess powerful immunosuppressive ability and can effectively inhibit the development and progression of EAE in different strains of mice. [ABSTRACT FROM AUTHOR]

Recently B-cell activating factor (BAFF) was identified by our group and others as a novel therapeutic target for the treatment of autoimmune diseases. To expand upon this, we utilized microarrays to screen for molecules upregulated in B cells from BAFF-inhibited mice with lupus-like disease and identified metabotropic glutamate receptor 3 (Grm3). In addition to confirming the expression of this receptor in B cells, a synthetic agonist of Grm3 was found to downregulate B cells and ameliorate autoimmune symptoms in mice. Conversely, a Grm3 antagonist increased B-cell numbers and further aggravated disease. Thus, these results suggest that activation of Grm3 ameliorates lupus-like disease in mice by reducing B cell numbers. Not only do the findings presented in this study increase our understanding of the inhibitory signals initiated on the surface of B cells, but they also identify a novel potential target for the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]