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TLR4 supports the expansion of FasL + CD5 + CD1d hi regulatory B cells, which decreases in contact hypersensitivity.
- Source :
-
Molecular immunology [Mol Immunol] 2017 Jul; Vol. 87, pp. 188-199. Date of Electronic Publication: 2017 May 12. - Publication Year :
- 2017
-
Abstract
- Certain B cells termed as "regulatory B cells" (Bregs) can suppress the ongoing immune responses and a splenic CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> Breg subset identified earlier was shown to exert its regulatory functions through secretion of IL-10. Though FasL expression is an alternative mechanism of immune suppression used by B cells, little is known about the FasL expressing CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> Bregs. In this study, we isolated splenocytes or splenic CD19 <superscript>+</superscript> B cells and compared the efficiency of toll-like receptor(TLR)4 ligand (lipopolysaccharide) with TLR9 ligand (CpG), anti-CD40 and TLR9 ligand (CpG) plus anti-CD40 on the FasL expression of splenic CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> Bregs by flow cytometry. FasL expression in CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> B cells was rapidly increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40 combinations failed to stimulate FasL expression in CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> B cells although the IL-10 production was up-regulated in this subset. In addition, LPS and other B10-cell inducers increased the expression of surface molecules like CD86 and CD25, which are correlated to the regulatory functions of B cells. Furthermore, NF-κB and NF-AT inhibitors decreased the TLR4-activated FasL expression in CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> B cells. Then we sorted splenic CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> Bregs using flow cytometry and found that TLR4-activated CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> Bregs suppressed the proliferation of CFSE-labeled CD4 <superscript>+</superscript> T cells in vitro, which was partly blocked by anti-FasL antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL expression in splenic CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> B cells was decreased compared to the control group after TLR4 ligation. Our findings suggest that the regulatory function of CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> B cells could be partly mediated by Fas-FasL pathway and this FasL expressing CD5 <superscript>+</superscript> CD1d <superscript>hi</superscript> Bregs might participate in the regulation of inflammatory diseases.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Cell Proliferation physiology
Cells, Cultured
Female
Inflammation metabolism
Interleukin-10 metabolism
Mice
Mice, Inbred C57BL
NF-kappa B metabolism
T-Lymphocytes, Helper-Inducer metabolism
Antigens, CD1d metabolism
B-Lymphocytes, Regulatory metabolism
CD5 Antigens metabolism
Dermatitis, Contact metabolism
Fas Ligand Protein metabolism
Toll-Like Receptor 4 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 87
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 28505514
- Full Text :
- https://doi.org/10.1016/j.molimm.2017.04.016