IL-10–overexpressing B cells regulate innate and adaptive immune responses - 05/03/15
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Abstract |
Background |
Distinct human IL-10–producing B-cell subsets with immunoregulatory properties have been described. However, the broader spectrum of their direct cellular targets and suppressive mechanisms has not been extensively studied, particularly in relation to direct and indirect IL-10–mediated functions.
Objective |
The aim of the study was to investigate the effects of IL-10 overexpression on the phenotype and immunoregulatory capacity of B cells.
Methods |
Primary human B cells were transfected with hIL-10, and IL-10–overexpressing B cells were characterized for cytokine and immunoglobulin production by means of specific ELISA and bead-based assays. Antigen presentation, costimulation capacity, and transcription factor signatures were analyzed by means of flow cytometry and quantitative RT-PCR. Effects of IL-10–overexpresing B cells on Toll-like receptor–triggered cytokine release from PBMCs, LPS-triggered maturation of monocyte-derived dendritic cells, and tetanus toxoid–induced PBMC proliferation were assessed in autologous cocultures.
Results |
IL-10–overexpressing B cells acquired a prominent immunoregulatory profile comprising upregulation of suppressor of cytokine signaling 3 (SOCS3), glycoprotein A repetitions predominant (GARP), the IL-2 receptor α chain (CD25), and programmed cell death 1 ligand 1 (PD-L1). Concurrently, their secretion profile was characterized by a significant reduction in levels of proinflammatory cytokines (TNF-α, IL-8, and macrophage inflammatory protein 1α) and augmented production of anti-inflammatory IL-1 receptor antagonist and vascular endothelial growth factor. Furthermore, IL-10 overexpression was associated with a decrease in costimulatory potential. IL-10–overexpressing B cells secreted less IgE and potently suppressed proinflammatory cytokines in PBMCs, maturation of monocyte-derived dendritic cells (rendering their profile to regulatory phenotype), and antigen-specific proliferation in vitro.
Conclusion |
Our data demonstrate an essential role for IL-10 in inducing an immunoregulatory phenotype in B cells that exerts substantial anti-inflammatory and immunosuppressive functions.
Le texte complet de cet article est disponible en PDF.Key words : IL-10 overexpression, regulatory B cells, immune regulation, anti-inflammatory effects, immunoregulatory capacity
Abbreviations used : APC, BLIMP-1, Br1, DC, FITC, GARP, G-CSF, IL-1Ra, IRF-4, MDDC, MIP, PD-L1, PE, SOCS, TLR, TLR-L, TT, VEGF, XBP-1
Plan
Supported by the Swiss National Science Foundation (grant no. 320030-125249/1, 32-188226, 320030-140772), the Christine Kühne-Center for Allergy Research and Education (CK-CARE), and the European Commission's Seventh Framework Programme (grant agreement no. 261357 MeDALL). |
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Disclosure of potential conflict of interest: C. A. Akdis has consultant arrangements with Actellion, Aventis, Stallergenes, Allergopharma, and Circacia; is employed by the Swiss Institute of Allergy and Asthma Research, University of Zurich; and has received research support from Novartis, PREDICTA: European Commission's Seventh Framework, the Swiss National Science Foundation, MeDALL: European Commission's Seventh Framework, and the Christine Kühne-Center for Allergy Research and Education. M. Akdis has received research support from the Swiss National Science Foundation and the European Commission's Seventh Framework Programme. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 135 - N° 3
P. 771 - mars 2015 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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