Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD.

Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis

“…Systemic administration of rGal-1 also markedly reduced plasma IL-17A levels compared to the untreated AD group, an important cytokine biomarker for AD patients [20,21]. In a previous mouse model, splenocytes isolated from OVAinduced AD BALB/c mice had significantly increased levels of IL-4, IL-5, IFN-γ and IL-17 after 72 h of OVA stimulation in vitro, whereas unstimulated cells were not significantly different than control animals [22]. Furthermore, in oxazolone-induced AD IL-17-null mice exhibit reduction of skin edema, eosinophilia, IL-4 and IL-13 production in skin and lymph nodes relative to wild-type animals [19,23].…”

Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model

“…Increased proportions of Foxp3 + CD4 + Tregs were found in patients treated with immunotherapy [23,24]. Additionally, induction of Tregs in murine models has been postulated to be an essential step in allergen-specific immunotherapy [25][26][27][28]. In 2012, Maazi et al demonstrated that the effects of allergen-specific immunotherapy can be partially explained by Tregs because depletion of Tregs only partially abrogated the suppressive effects induced by the therapy [58].…”

“…We have previously demonstrated that kakkonto suppresses the occurrence of allergic symptoms in a murine FA model [21] and kakkonto induces Foxp3 + CD4 + regulatory T cells (Tregs) in the colon as a novel mechanism underlying the therapeutic action [22]. It is reported that allergen-specific immunotherapy increases the production of local and systemic Foxp3 + CD4 + Tregs as an essential step in patients [23,24] and experimental models [25][26][27][28]. Therefore, we hypothesized that kakkonto might have a potential as a therapeutic drug for the treatment of immune diseases induced by the disruption of intestinal mucosal tolerance, such as FAs.…”

Hypoallergenic acid-sensitive modification preserves major mugwort allergen fold and delivers full repertoire of MHC class II-binding peptides during endolysosomal degradation

“…The puried allergen, Art v 1, was modied with cis-aconitic anhydride, which reacts with free amino groups (lysine and free N-terminus) on proteins similar to a reaction with other acid anhydrides, 20 resulting in a monomeric modied protein that is able to bypass mucosal barriers if applied locally. 21 However, cis-aconitylation is a reversible modication due to acyl group hydrolysis under acidic conditions, 8,9,22 and hence during processing in endolysosomal compartments, the allergen completely recovers its native structure.…”