Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production

Ikizawa, Koichi; Kondo, Keiichi; Koshio, Takehiro; Matsuura, Naosuke; Yanagihara, Yukiyoshi

doi:10.1111/j.1365-2249.1995.tb03710.x

Cited by 19 publications

(3 citation statements)

References 40 publications

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“…IL‐4 leads to up‐regulation of MHC‐II, CD23 on B cells and induction of IgE production 23, 24, 36, 37. Similar effects were observed in studies assessing the effects of IL‐4 and IL‐13 in human B cells 38–40. IL‐4 is not only a major B‐cell activating factor that is effectively produced by helper CD4 + T cells but, through a positive feedback loop, it reinforces T H 2 polarization of CD4 + T cells 41 thus contributing to increase IL‐4 in LNs of CCR7 −/− mice.…”

Section: Discussionmentioning

confidence: 71%

Deficient CCR7 signaling promotes T_H2 polarization and B‐cell activation in vivo

et al. 2011

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The chemokine receptor CCR7 has a central role in regulating homing and positioning of T cells and DCs to lymph nodes (LNs) and participates in T-cell development and activation. In this study, we addressed the role of CCR7 signaling in T H 2 polarization and B-cell activation. We provide evidence that the lack of CCR7 drives the capacity of naïve CD4 1 T cells to polarize toward T H 2 cells. This propensity contributes to a lymph node environment in CCR7-deficent mice characterized by increased expression of IL-4 and increased frequency of T H 2 cells. We show that elevated IL-4 levels lead to B-cell activation characterized by up-regulated expression of MHC class II, CD23 and CD86. Activated B cells are in turn highly efficient in presenting antigen to CD41 T cells and thus potentially contribute to the T H 2 microenvironment. Taken together, our results support the idea of a CCR7-dependent patterning of T H 2 responses, with absent CCR7 signaling favoring T H 2 polarization, dislocation of T helper cells into the B-cell follicles and, as a consequence, B-cell activation. 48soluble factors. Moreover, in addition to the well-established role of CCR7 as a homing receptor directing the migration of cells into SLOs, increasing evidence suggests that CCR7-mediated signals contribute to other cellular processes such as modulation of cell proliferation, activation or differentiation [10][11][12].In the present study, we reveal the mechanisms that cause B-cell activation in the non-inflamed LNs in CCR7 À/À mice.

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Section: Discussionmentioning

confidence: 71%

Deficient CCR7 signaling promotes T_H2 polarization and B‐cell activation in vivo

et al. 2011

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“…For instance, in anti-viral treatment, in the control of cancer cell growth, in targeting specific T cell receptor gene V regions, and in the selective inhibition of particular cytokines and adhesion molecules. For example, IL-4-specific ODN have been used to block IgE production in rodents in vitro [32] and an IL-4 receptor ODN was able to inhibit human lL-4 receptor expression in vitro [11]. It may be envisaged that the lag between the basic research and the clinical benefit will be shortened by the application of ODN technology.…”

Section: Therapeutic Potentialmentioning

confidence: 99%

“…Provided that the relevant gene sequences are known, there is very wide choice of gene targets, including intracellular, membrane-bound and soluble molecules of mammalian cells, bacteria and viruses. In this issue of Clinical and Experimental Immunology, Ikizawa et al [11] describe the use of ODN to block IL-4 receptor expression and IgE synthesis by peripheral blood B cells. This editorial assesses ODN and their therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of gene expression by anti-sense oligodeoxynucleotides

Zheng¹,

Kemeny

1995

Clinical and Experimental Immunology

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Insect venom immunotherapy induces interleukin‐10 production and a Th2‐to‐Th1 shift, and changes surface marker expression in venom‐allergic subjects

Bellinghausen¹,

Metz²,

Enk³

et al. 1997

Eur J Immunol

245

186

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The current study was carried out to elucidate the immunoregulatory changes induced by venom immunotherapy (VIT) in bee or wasp allergic subjects. All subjects included in this study had a history of severe systemic allergic reactions to stings of the respective insect as well as positive skin tests with the respective venom or venom-specific IgE in the sera. Parameters assessed in peripheral blood mononuclear cells (PBMC) before and after initiation of VIT (rush therapy reaching a maintenance dose of 100 micrograms venom injected subcutaneously within 1 week) were expression of CD3, CD4, CD8, CD45RA, CD45RO, interleukin (IL)-2 receptor (R) alpha, IL-4R, IL-12R, Fc epsilon RII, CD40, and CD40 ligand (CD40L), cells producing interferon (IFN)-gamma and IL-10 after stimulation with phorbol 12-myristate 13-acetate + ionomycin in the presence of monensin measured by flow cytometry; secretion of IFN-gamma, IL-4, and IL-10 measured by ELISA (IFN-gamma and IL-10 were additionally measured by PCR), and proliferation after stimulation with the respective venom. Significant decreases were observed after VIT for proliferative response to venom and venom + IL-4, IL-4 secretion, Fc epsilon RII, CD40, and CD40L expression. Significant increases were observed after VIT for IFN-gamma concerning the amount secreted and the number of producing cells, and IL-10, IL-10 was mainly produced by CD4+ cells that were negative for IFN-gamma, but some double-positive (IL-10 and IFN-gamma) cells were always detected. Addition of blocking anti-IL-10 antibodies, but not isotype control antibodies, prevented down-regulation of proliferation (but not IL-4 secretion) and further enhanced IFN-gamma secretion after VIT. These data indicate that in insect venom allergic subjects, VIT not only induces a rapid shift in cytokine expression from Th2 to Th1 cytokines, but also leads to induction of the immunosuppressive cytokine IL-10, which may be important for the limitation of potentially harmful allergen-specific Th1 responses. The described changes in cytokine expression may be responsible for subsequent increases in allergen-specific IgG and decreases in IgE production, as well as suppressive activity observed in earlier studies.

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Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production

Cited by 19 publications

References 40 publications

Deficient CCR7 signaling promotes T_H2 polarization and B‐cell activation in vivo

Deficient CCR7 signaling promotes T_H2 polarization and B‐cell activation in vivo

Inhibition of gene expression by anti-sense oligodeoxynucleotides

Insect venom immunotherapy induces interleukin‐10 production and a Th2‐to‐Th1 shift, and changes surface marker expression in venom‐allergic subjects

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Inhibition of IL-4 receptor up-regulation on B cells by antisense oligodeoxynucleotide suppresses IL-4-induced human IgE production

Cited by 19 publications

References 40 publications

Deficient CCR7 signaling promotes TH2 polarization and B‐cell activation in vivo

Deficient CCR7 signaling promotes TH2 polarization and B‐cell activation in vivo

Inhibition of gene expression by anti-sense oligodeoxynucleotides

Insect venom immunotherapy induces interleukin‐10 production and a Th2‐to‐Th1 shift, and changes surface marker expression in venom‐allergic subjects

Contact Info

Product

Resources

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Deficient CCR7 signaling promotes T_H2 polarization and B‐cell activation in vivo

Deficient CCR7 signaling promotes T_H2 polarization and B‐cell activation in vivo