2018-06-01·Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery
[CD23 on B cells determines Breg-facilitated IL-10 secretion as well as activation of T cells].
作者: Q Chen ; Y P Ba ; M H Zhou ; S D Li ; P W Zhang
Objective:To explore whether or not the IL-10 mediated by Bregs modulate the secreting T cells activation by the anti-CD23 antibody, to find a new target for the treatment of allergic rhinitis. Method:The rat model of allergic rhinitis was established. Anti-CD23 antibody was used to observe the behavioral changes, passive skin allergen test, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, immunofluorescence and flow cytometry serological indicators, systemic and nasal mucosa. Result:Compared with the blank control group, allergic rhinitis group rats sneezing, flexible nose, runny nose, subcutaneous mass increases;The levels of IL-10, IFN-γ and Bregs in blood decreased, the levels of IL-4, CD23+ B cells and CD4+ T cells increased;Nasal mucosa CD23 fluorescence intensity increased, CD19 and IL-10 fluorescence intensity decreased. Compared with the allergic rhinitis group, the number of sneezing, the frequency of nasal flexion, the symptoms of runny nose and the subcutaneous mass in the antibody intervention group were significantly improved;The levels of IL-10 in the blood, IFN-γ, the percentage of Bregs cells in whole blood increased, the levels of IL-4, CD23+ B cells and CD4+ T cells decreased;Nasal mucosa CD23 fluorescence intensity decreased, CD19 and IL-10 fluorescence intensity increased. There is little difference between the two routes of administration. Conclusion:The enhanced expression of CD23 on B cells is involved in the development of allergic rhinitis. The anti-CD23 antibody may control the symptoms and signs of allergic rhinitis. There is no significant difference between subcutaneous administration and improved nasal-drip way. As the preferred method of anti-CD23 antibody application, anti-CD23 is expected to become a new method to control and treat allergic rhinitis. Anti-CD23 antibodies can exert a therapeutic effect by T cell activation,which rely on the Bregs-mediated secretion of IL-10.
2016-11-01·EBioMedicine1区 · 医学
Commensal Microbe-specific Activation of B2 Cell Subsets Contributes to Atherosclerosis Development Independently of Lipid Metabolism.
1区 · 医学
作者: Lin Chen ; Tomoaki Ishigami ; Rie Nakashima-Sasaki ; Tabito Kino ; Hiroshi Doi ; Shintaro Minegishi ; Satoshi Umemura
The relation between B2 cells and commensal microbes during atherosclerosis remains largely unexplored. Here we show that under hyperlipidemic conditions intestinal microbiota resulted in recruitment and ectopic activation of B2 cells in perivascular adipose tissue, followed by an increase in circulating IgG, promoting disease development. In contrast, disruption of the intestinal microbiota by a broad-spectrum antibiotic cocktail (AVNM) led to the attenuation of atherosclerosis by suppressing B2 cells, despite the persistence of serum lipid abnormalities. Furthermore, pharmacological depletion of B2 cells with an anti-B2-cell surface CD23 antibody also attenuated commensal microbe-induced atherosclerosis. Moreover, expression analysis of TLR-signaling-related genes in the activated B2 cell subsets, assessed using the Toll-Like Receptor Signaling Pathway RT2 Profiler PCR Array, confirmed activation of the B2-cell autoantibody-production axis, which was associated with an increased capacity of B2 cells to bind to intestinal microbiota. Together, our findings reveal the critical role of commensal microbe-specific activation of B2 cells in the development of atherogenesis through lipid metabolism-independent mechanisms.
2015-12-01·Immunity, Inflammation and Disease4区 · 医学
High affinity targeting of CD23 inhibits IgE synthesis in human B cells
4区 · 医学
作者: Fellmann, Marc ; Buschor, Patrick ; Roethlisberger, Silvan ; Zellweger, Fabian ; Vogel, Monique
The low-affinity IgE receptor FcϵRII (CD23) is part of the regulatory system controlling IgE synthesis in human B cells and exists in membrane and soluble forms. Binding of IgE to CD23 has been described to have stabilizing effects and to prevent cleavage of CD23. Previous experiments using anti-CD23 antibodies reduced IgE synthesis but were difficult to interpret as the antibody Fc part might also mediate feedback mechanisms. The purpose of this study was to investigate the regulatory role of CD23, by using designed ankyrin repeat proteins (DARPins) that specifically recognize CD23. Anti-CD23 DARPins were isolated by ribosome display and were produced as monovalent and bivalent constructs. Affinities to CD23 were measured by surface plasmon resonance. IgE synthesis and up-regulation of CD23 in human peripheral B cells were induced by IL-4 and anti-CD40 antibody. We assessed CD23 expression and its stabilization by FACS and used an ELISA for detecting soluble CD23. IgE synthesis was measured by ELISA and real-time PCR. Surface plasmon resonance revealed affinities of the DARPins to CD23 in the pico-molar range. Anti-CD23 DARPins strongly inhibited binding of IgE to CD23 and share thus a similar binding epitope as IgE. The DARPins stabilized membrane CD23 and reduced IgE synthesis in an isotype specific manner. Furthermore, the anti-CD23 DARPins decreased IgE transcript through inhibition of mature Cϵ RNA synthesis suggesting a posttranscriptional control mechanism. This study demonstrates that targeting CD23 alone is sufficient to inhibit IgE synthesis and suggests that a negative signaling occurs directly through the CD23 molecule.