Immunostimulatory DNA inhibits IL-4–dependent IgE synthesis by human B cells

Horner, Anthony A.; Widhopf, George F.; Burger, Jan A.; Takabayashi, Kenji; Cinman, Nadya; Ronaghy, Arash; Spiegelberg, Hans L.; Raz, Eyal

doi:10.1067/mai.2001.117795

Cited by 41 publications

(41 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…24,25 We and others have previously shown that ISS-ODN elicits innate cytokine responses from several cell types including macrophages, dendritic cells, natural killer cells, and B cells, but not T cells. [26][27][28] However, several of these cytokines, including IL-10, IL-12, type 1 IFNs, and IFN-c, are known to inhibit the functionality of Th2 cells. In our published studies we found that naı¨ve mice injected with ISS-ODN have elevated serum IL-12 and IFN-c levels for a week or more.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, we have published that ISS-ODN exposure down-regulates IL-4 receptor and up-regulates IFN-c receptor expression on B cells. 27 Therefore, ISS-ODN may also inhibit the functions of effector cells of the late phase AR hypersensitivity response by rendering them resistant to the effects of Th2 cytokines, including IL-4, while increasing their responsiveness to IFN-c.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Allergen‐independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis

Rhee

Libet²,

Chisholm³

et al. 2004

Immunology

Self Cite

View full text Add to dashboard Cite

SUMMARYWhile effective for the prevention and treatment of allergic rhinitis (AR) symptoms, currently available medications do not reverse allergen specific hypersensitivities. Therefore, pharmacotherapeutics are not curative and their daily use is often required for years. These investigations were conducted to determine whether immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) delivery protects previously sensitized mice from AR hypersensitivity responses and modulates their allergen specific immune profiles. Mice were first sensitized with ovalbumin (OVA) and alum, twenty-four hr before beginning a series of seven daily intranasal (i.n.) allergen challenges, subsets of mice received a single i.n. or intradermal (i.d.) dose of ISS-ODN or control oligodeoxynucleotide (C-ODN), a single intraperitoneal (i.p.) injection of dexamethasone (DXM), or no intervention. Mice receiving i.d. or i.n. ISS-ODN were found to have attenuated immediate and late phase effector cell responses to i.n. OVA challenge. Specifically, ISS-ODN treated mice had less histamine and cysteinyl leukotriene release and eosinophilic inflammation in their nasal passages than mice treated with C-ODN. In addition, splenocytes from ISS-ODN but not C-ODN treated mice displayed attenuated OVA-specific interleukin (IL)-4, IL-5, and IL-13 but increased interferon-c responses. Finally, ISS-ODN was generally a more effective treatment than DXM, both in blunting AR hypersensitivity responses and in shifting T helper 2 Th2-biased immune parameters towards Th1 dominance. As ISS-ODN delivery rapidly attenuated effector cell responses in this AR model in an allergen independent manner, the present results suggest that therapy with ISS-ODN alone may be an effective alternative to corticosteroid medications for the clinical management of AR.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Allergen‐independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis

Rhee

Libet²,

Chisholm³

et al. 2004

Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…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). In addition to inducing Th1 responses, ISS also inhibits expression of Th2 cytokines in the lung including IL-4 (2, 12), IL-5 (1), IL-9 (12), and IL-13 (13), while also reducing levels of expression of Th2 cytokine receptors such as the IL-4R (11).…”

mentioning

confidence: 99%

“…ISS also up-regulates the expression of Th1 cytokine receptors such as the IFN-␥ receptor (11). In addition to inducing Th1 responses, ISS also inhibits expression of Th2 cytokines in the lung including IL-4 (2, 12), IL-5 (1), IL-9 (12), and IL-13 (13), while also reducing levels of expression of Th2 cytokine receptors such as the IL-4R (11). The immunomodulatory effect of ISS is due to its effect on cells that express TLR-9 (14) the receptor for ISS, in particular dendritic cells, as well as macrophages, and B cells.…”

mentioning

confidence: 99%

Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

Youn

Miller

Baek

et al. 2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Monophosphoryl lipid A, a nontoxic derivate of LPS of Salmonella minnesota, mixed with grass pollen extract enhanced the production of IFN-␥ and reduced the production of IL-5 in PBMC from grass pollen-allergic patients (16). Synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) derived from bacterial DNA promoted Th1-like cytokine production and decreased the spontaneous synthesis of IgE Abs in allergic individuals in vitro (17)(18)(19)(20). This immunomodulatory capacity was even more pronounced when CpG-ODN were chemically linked to a single defined allergen (21)(22)(23).…”

mentioning

confidence: 99%

A Novel Approach to Specific Allergy Treatment: The Recombinant Allergen-S-Layer Fusion Protein rSbsC-Bet v 1 Matures Dendritic Cells That Prime Th0/Th1 and IL-10-Producing Regulatory T Cells

Gerstmayr

Ilk

Schabussova

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

An ideal vaccine for allergen-specific immunotherapy of type I allergies should display reduced mediator-releasing capacity, induce maturation of APC, and modify the disease-eliciting Th2-dominated allergen-specific response to a more physiological response. We have previously shown that rSbsC-Bet v 1, the recombinant fusion protein of a bacterial surface (S-layer) protein of Geobacillus stearothermophilus ATCC 12980 and the major birch pollen allergen Bet v 1, exhibited reduced allergenicity and induced IFN-γ and IL-10 synthesis in Bet v 1-specific Th2 clones. In this study, we characterized the effects of rSbsC-Bet v 1 on immature monocyte-derived dendritic cells (mdDC) and the consequences for the polarization of naive CD4+ T lymphocytes isolated from the blood of birch pollen-allergic patients. mdDC responded to rSbsC-Bet v 1 with a significant up-regulation of costimulatory molecules, functional maturation, and the synthesis of IL-10 and IL-12. mdDC matured with rSbsC-Bet v 1 induced the differentiation of naive T cells into IFN-γ-producing cells. This effect was IL-12 dependent. In parallel, a substantial number of naive T cells developed into IL-10-producing CD25+Foxp3+CLTA-4+ cells capable of active suppression. Thus, rSbsC-Bet v 1 showed immune stimulatory capacity on DC, which then promoted the simultaneous differentiation of Th0/Th1 cells and regulatory T cells. These data further support that the concept of conjugating allergens to bacterial agents is a promising approach to improve vaccines for specific immunotherapy of atopic allergies.

show abstract

Immunostimulatory DNA inhibits IL-4–dependent IgE synthesis by human B cells

Cited by 41 publications

References 35 publications

Allergen‐independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis

Allergen‐independent immunostimulatory sequence oligodeoxynucleotide therapy attenuates experimental allergic rhinitis

Immunostimulatory DNA Reverses Established Allergen-Induced Airway Remodeling

A Novel Approach to Specific Allergy Treatment: The Recombinant Allergen-S-Layer Fusion Protein rSbsC-Bet v 1 Matures Dendritic Cells That Prime Th0/Th1 and IL-10-Producing Regulatory T Cells

Contact Info

Product

Resources

About