IL-10-producing regulatory B cells exhibit functional defects and play a protective role in severe endotoxic shock. (October 2019)

• Record Type: Journal Article
• Authors: Tao, Lei; Wang, Yiyuan; Xu, Jialan; Su, Jianbing; Yang, Qin; Deng, Wende; Zou, Binhua; Tan, Yanhui; Ding, Zongbao; Li, Xiaojuan
• Is Part Of: Pharmacological research. Volume 148(2019)
• Publication Date: 2019-10
• Subjects: LPS lipopolysaccharide -- Breg regulatory B cells -- MZ marginal zone -- GM-CSF granulocyte-macrophage colony stimulating factor -- PBS phosphate buffered saline -- q-PCRs quantitative PCRs -- GO gene ontology -- ELISA enzyme-linked immunosorbent assay -- TLR toll-like receptor -- CD cluster differentiation -- FasL Fas ligand -- CFSE 5(6)-CFDA N-succinimidyl ester -- MFI mean fluorescence intensity; Lipopolysaccharide (PubChem CID: 11970143) -- Haematoxylin (PubChem CID: 442514) -- Eosin (PubChem CID: 11048) -- Phorbol 12-myristate 13-acetate (PMA, PubChem CID: 27924) -- Ionomycin (PubChem CID: 6912226) -- Monensin (PubChem CID: 441145) -- 5(6)-CFDA N-succinimidyl ester (CFSE, PubChem, CID: 71314542); Endotoxic shock -- Regulatory B cells -- CD1d -- IL-10 -- CD4+ T cells; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2019.104457
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Dysregulated host immune homeostasis in sepsis is life-threatening even after a successfully treated bacterial infection. Lipopolysaccharide (LPS) is an endotoxin that is a major contributor to the aberrant immune responses and endotoxic shock in gram-negative bacterial sepsis. However, the current knowledge of the role of B cells in endotoxic shock is limited. Here, we report that CD1d expression in B cells and the percentage of CD5 + CD1d hi regulatory B (Breg) cells decreased in a mouse model of endotoxic shock. Interestingly, IL-10 but not FasL expression in CD5 + CD1d hi Breg cells in response to endotoxin was dramatically reduced in severe septic shock mice, and the regulatory function of CD5 + CD1d hi Breg cells in vitro to control the Th1 response was also diminished. Adoptive transfer of CD5 + CD1d hi Breg cells from healthy WT mice but not IL-10 deficient mice downregulated the IFN-γ secretion in CD4 + T cells and conferred protection against severe endotoxic shock in vivo. Our findings demonstrate the change and notable therapeutic potential of IL-10-producing Breg cells in endotoxic shock.