Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B lymphocytes have critical roles as positive and negative regulators of immunity. Their inhibitory function has been associated primarily with interleukin 10 (IL-10) because B-cell-derived IL-10 can protect against autoimmune disease and increase susceptibility to pathogens. Here we identify IL-35-producing B cells as key players in the negative regulation of immunity. Mice in which only B cells did not express IL-35 lost their ability to recover from the T-cell-mediated demyelinating autoimmune disease experimental autoimmune encephalomyelitis (EAE). In contrast, these mice displayed a markedly improved resistance to infection with the intracellular bacterial pathogen Salmonella enterica serovar Typhimurium as shown by their superior containment of the bacterial growth and their prolonged survival after primary infection, and upon secondary challenge, compared to control mice. The increased immunity found in mice lacking IL-35 production by B cells was associated with a higher activation of macrophages and inflammatory T cells, as well as an increased function of B cells as antigen-presenting cells (APCs). During Salmonella infection, IL-35- and IL-10-producing B cells corresponded to two largely distinct sets of surface-IgM(+)CD138(hi)TACI(+)CXCR4(+)CD1d(int)Tim1(int) plasma cells expressing the transcription factor Blimp1 (also known as Prdm1). During EAE, CD138(+) plasma cells were also the main source of B-cell-derived IL-35 and IL-10. Collectively, our data show the importance of IL-35-producing B cells in regulation of immunity and highlight IL-35 production by B cells as a potential therapeutic target for autoimmune and infectious diseases. This study reveals the central role of activated B cells, particularly plasma cells, and their production of cytokines in the regulation of immune responses in health and disease.
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PMID:IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. 2457 63

B-cell activating factor (BAFF) is regarded as a new therapeutic target in autoimmune diseases such as systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Along with other researchers, we have demonstrated that BAFF inhibitor atacicept (TACI-IgG) suppresses lupus and experimental allergic encephalomyelitis (EAE) by reducing the mature B-cell number but not memory B cells. It is however unclear whether TACI-Ig affects pathogenic T cells and memory T cells. In the present study, we found that blocking BAFF with TACI-IgG effectively reduces the pathogenic Th1 and Th17 cells in EAE mice. However, TACI-IgG did not reduce memory CD62L(+)CD44(hi)CD4(+) and CD62L(+)CD44(hi)CD8(+) T cells in EAE mice. When interleukin (IL)-15 was neutralized, memory CD62L(+)CD44(hi) T cells were significantly reduced in TACI-IgG-treated EAE mice. These results suggest that TACI-IgG is effective in effective controlling Th1 and Th17 cells, but it also increases IL-15 to upregulate memory T cells in EAE mice. The study provides hints for the clinical application of the combination of BAFF- and IL-15-specific therapeutic agents.
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PMID:Blockade of B-cell activating factor with TACI-IgG effectively reduced Th1 and Th17 cells but not memory T cells in experimental allergic encephalomyelitis mice. 2655 26

B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10-B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10+ Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10+B cells over IL-10-B cells under noninflammatory conditions in vitro, whereas it expanded IL-10-B cells over IL-10+B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10-B cells over IL-10+B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10-B cells over IL-10+ regulatory B cells via BAFF receptors in inflammatory responses.
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PMID:B cell activating factor (BAFF) selects IL-10-B cells over IL-10+B cells during inflammatory responses. 2819 52