DNA‐based immunotherapeutics for the treatment of allergic disease

Horner, Anthony A.; Uden, John H. Van; Zubeldía, J M; Broide, David H.

doi:10.1034/j.1600-065x.2001.790111.x

Cited by 93 publications

(52 citation statements)

References 3 publications

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“…These remarkable immunostimulatory properties of short CpG-ODNs, and mostly of those with a phosphorothioate-stabilized backbone (3), have suggested a possible therapeutic use as vaccine adjuvants for prevention of viral, bacterial, or parasitic diseases. CpG-ODNs, when used in vaccination trials in healthy human volunteers (4,5) and in immunocompromised, HIV-infected patients (6), manifested strongly enhanced vaccination efficiency (7,8). An antitumor activity for CpG-ODNs has also been advocated when CpG-ODNs are used either alone or in combination with chemotherapy (9,10).…”

mentioning

confidence: 99%

A GpC-Rich Oligonucleotide Acts on Plasmacytoid Dendritic Cells To Promote Immune Suppression

Volpi

Fallarino

Bianchi

et al. 2012

The Journal of Immunology

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Short synthetic oligodeoxynucleotides (ODNs) rich in CpG or GpG motifs have been considered as potential modulators of immunity in clinical settings. In this study, we show that a synthetic GpC-ODN conferred highly suppressive activity on mouse splenic plasmacytoid dendritic cells, demonstrable in vivo in a skin test assay. The underlying mechanism involved signaling by noncanonical NF-κB family members and TGF-β–dependent expression of the immunoregulatory enzyme IDO. Unlike CpG-ODNs, the effects of GpC-ODN required TLR7/TRIF-mediated but not TLR9/MyD88-mediated events, as do sensing of viral ssRNA and the drug imiquimod. Induction of IDO by a GpC-containing ODN could also be demonstrated in human dendritic cells, allowing those cells to assist FOXP3+ T cell generation in vitro. Among potentially therapeutic ODNs, this study identifies GpC-rich sequences as novel activators of TLR7-mediated, IDO-dependent regulatory responses.

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mentioning

confidence: 99%

A GpC-Rich Oligonucleotide Acts on Plasmacytoid Dendritic Cells To Promote Immune Suppression

Volpi

Fallarino

Bianchi

et al. 2012

The Journal of Immunology

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“…The mechanism by which ISS inhibits airway inflammation in mouse models of asthma is incompletely understood. The immune response to ISS is characterized by the expression of cytokines including IFNs (␣, ␤, and ␥), IL-6, IL-10, and IL-12 (10). ISS also up-regulates the expression of Th1 cytokine receptors such as the IFN-␥ receptor (11).…”

mentioning

confidence: 99%

Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

Youn

Miller

Baek

et al. 2004

The Journal of Immunology

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To determine whether immunostimulatory sequences of DNA (ISS) can reverse established airway remodeling, mice that had developed airway remodeling following 3 mo of repetitive OVA challenges, were treated with ISS for 1–3 mo. Systemic administration of ISS to mice that had already developed established airway remodeling significantly reduced the degree of airway collagen deposition (assessed by lung collagen content, peribronchial trichrome staining, and immunostaining with anticollagen type III and type V Abs). ISS reduced bronchoalveolar lavage and lung levels of TGF-β1 and reduced the number of TGF-β1-positive eosinophils and TGF-β1-positive mononuclear cells recruited to the airway. In vitro studies demonstrated that ISS inhibited TGF-β1 expression by macrophages (RAW 264.7 cell line and bone marrow-derived macrophages). In addition, ISS significantly reduces lung levels of expression of the chemokine thymus- and activation-regulated chemokine, as well as the number of peribronchial CD4+ lymphocytes that express Th2 cytokines that promote peribronchial fibrosis. Overall, these studies demonstrate that ISS can reverse features of airway collagen deposition by reducing levels of lung TGF-β1, as well as by reducing levels of the chemokine thymus- and activation-regulated chemokine and the numbers of peribronchial CD4+ lymphocytes that drive the ongoing Th2 immune response.

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“…Of note, two studies on SCIT claimed a fundamental role in inducing such effect (28,29) and similar observations were reported with SLIT (30). In fact, in a study on SLIT with a birch pollen extract, a regulatory T-cell suppression through IL-10 during the early phase and immune deviation of allergen-specific T cells during the late phase of treatment were described, leading to conclusions that SLIT induces immune mechanisms comparable with…”

Section: Effects On T Cells and Cytokinesmentioning

confidence: 63%

Inflammation in Respiratory Allergy Treated by Sublingual Immunotherapy

et al. 2009

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The most common allergic diseases, such as rhinitis, asthma and atopic dermatitis, are sustained by allergic inflammation, the treatment of which requires anti-inflammatory activity. Among the available treatments, allergen immunotherapy (IT) has a documented impact on allergic inflammation which persists after its discontinuation and modifies the natural course of allergy. The anti-inflammatory effects of IT, and particularly of sublingual IT (SLIT), are based on the ability to modify the phenotype of T cells which, in allergic subjects, are characterized by a prevalence of the Th2 type, with production of IL-4, IL-5, IL-13, IL-17, and IL-32 cytokines. IT-induced changes result in a Th1-type response (immune deviation) related to an increased IFN-gamma and IL-2 production or in a Th2 reduced activity, through a mechanism of anergy or tolerance. It is now known that T cell tolerance is characterized by the generation of allergen-specific Treg cells, which produce cytokines such as IL-10 and TGF-beta with immunosuppressant and/or immunoregulatory activity. Recent studies suggest that the anti-inflammatory mechanism of SLIT is similar to classical, subcutaneous IT, with a prominent role in SLIT for mucosal dendritic cells. The tolerance pattern induced by Treg accounts for the suppressed or reduced activity of inflammatory cells and for the isotypic switch of antibody synthesis from IgE to IgG, and especially to IgG4. Data obtained from biopsies clearly indicate that the pathophysiology of the oral mucosa plays a pivotal role in inducing tolerance to the sublingually administered allergen.

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DNA‐based immunotherapeutics for the treatment of allergic disease

Cited by 93 publications

References 3 publications

A GpC-Rich Oligonucleotide Acts on Plasmacytoid Dendritic Cells To Promote Immune Suppression

A GpC-Rich Oligonucleotide Acts on Plasmacytoid Dendritic Cells To Promote Immune Suppression

Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

Inflammation in Respiratory Allergy Treated by Sublingual Immunotherapy

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