TLR4 supports the expansion of FasL+CD5+CD1dhi regulatory B cells,which decreases in contact hypersensitivity |
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| Institution: | 1. Laboratory of Anti-inflammatory Immunomodulatory Pharmacology, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China;2. Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China;3. Department of Clinical Pharmacy, The Affiliated Nanhai Hospital of Southern Medical University, Foshan 528200, PR China;1. Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain;2. Inmunotek, SL. Alcalá de Henares, Madrid, Spain;3. Department of Immunology, Hospital Clínico San Carlos, Madrid, Spain;4. Department of Microbiology I-Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain;1. Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China;2. Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China;1. Institute for Biochemical Research-Histology B-Pathology B, Faculty of Medicine, National University of La Plata, Argentina;2. CNRS UMR8147, Paris Descartes University, Paris, France;1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, China;2. Department of General Practice, Qilu Hospital of Shandong University, Ji’nan, China;3. Department of Geriatrics, Qilu Hospital of Shandong University, Ji’nan, China;4. Department of Emergency, Qilu Hospital of Shandong University, Ji’nan, China;1. La Jolla Institute for Allergy & Immunology, La Jolla, Calif;2. J. Craig Venter Institute, La Jolla, Calif;3. Department of Pathology, University of California, San Diego, Calif;4. National Jewish Health, Denver, Colo |
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| Abstract: | Certain B cells termed as “regulatory B cells” (Bregs) can suppress the ongoing immune responses and a splenic CD5+CD1dhi 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+CD1dhi Bregs. In this study, we isolated splenocytes or splenic CD19+ 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+CD1dhi Bregs by flow cytometry. FasL expression in CD5+CD1dhi B cells was rapidly increased after TLR4 ligation. Intriguingly, anti-CD40 and CpG plus anti-CD40 combinations failed to stimulate FasL expression in CD5+CD1dhi 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+CD1dhi B cells. Then we sorted splenic CD5+CD1dhi Bregs using flow cytometry and found that TLR4-activated CD5+CD1dhi Bregs suppressed the proliferation of CFSE-labeled CD4+ T cells in vitro, which was partly blocked by anti-FasL antibody. In oxazolone-sensitized mice having contact hypersensitivity, FasL expression in splenic CD5+CD1dhi B cells was decreased compared to the control group after TLR4 ligation. Our findings suggest that the regulatory function of CD5+CD1dhi B cells could be partly mediated by Fas-FasL pathway and this FasL expressing CD5+CD1dhi Bregs might participate in the regulation of inflammatory diseases. |
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| Keywords: | Regulatory B cell FasL TLR4 TLR9 Anti-CD40 Contact hypersensitivity |
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