The effects of resiquimod in an ovalbumin-induced allergic rhinitis model

Qu, Shenhong; Qin, Taijie; Li, Min; Zhang, Shaojie; Ye, Linsong; Wei, Jiazhang; Fan, Huifeng; Chen, Baiwen

doi:10.1016/j.intimp.2018.04.015

Cited by 9 publications

(6 citation statements)

References 43 publications

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“…CD8+ and NKT cells have been highlighted as sources for IFN-γ production ( 133 , 134 ). Resiquimod was demonstrated to reduce epithelial factors IL-25, IL-33, and IL-13 from the serum of OVA sensitised mice while promoting Th1 and Treg cell populations ( 135 ). Increased IgG2a has been observed as a protective mechanism, alongside reduced IgE, reduced IL-5, IL-4, and IL-13 ( 136 ).…”

Section: Intracellular Tlrsmentioning

confidence: 99%

Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy

et al. 2020

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Toll-like receptors (TLRs) are essential components of innate immunity and provide defensive inflammatory responses to invading pathogens. Located within the plasma membranes of cells and also intracellular endosomes, TLRs can detect a range of pathogen associated molecular patterns from bacteria, viruses and fungi. TLR activation on dendritic cells can propagate to an adaptive immune response, making them attractive targets for the development of both prophylactic and therapeutic vaccines. In contrast to conventional adjuvants such as aluminium salts, TLR agonists have a clear immunomodulatory profile that favours anti-allergic T lymphocyte responses. Consequently, the potential use of TLRs as adjuvants in Allergen Immunotherapy (AIT) for allergic rhinitis and asthma remains of great interest. Allergic Rhinitis is a Th2-driven, IgE-mediated disease that occurs in atopic individuals in response to exposure to otherwise harmless aeroallergens such as pollens, house dust mite and animal dander. AIT is indicated in subjects with allergic rhinitis whose symptoms are inadequately controlled by antihistamines and nasal corticosteroids. Unlike anti-allergic drugs, AIT is disease-modifying and may induce long-term disease remission through mechanisms involving upregulation of IgG and IgG4 antibodies, induction of regulatory T and B cells, and immune deviation in favour of Th1 responses that are maintained after treatment discontinuation. This process takes up to three years however, highlighting an unmet need for a more efficacious therapy with faster onset. Agonists targeting different TLRs to treat allergy are at different stages of development. Synthetic TLR4, and TLR9 agonists have progressed to clinical trials, while TLR2, TLR5 and TLR7 agonists been shown to have potent anti-allergic effects in human in vitro experiments and in vivo in animal studies. The anti-allergic properties of TLRs are broadly characterised by a combination of enhanced Th1 deviation, regulatory responses, and induction of blocking antibodies. While promising, a durable effect in larger clinical trials is yet to be observed and further long-term studies and comparative trials with conventional AIT are required before TLR adjuvants can be considered for inclusion in AIT. Here we critically evaluate experimental and clinical studies investigating TLRs and discuss their potential role in the future of AIT.

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Section: Intracellular Tlrsmentioning

confidence: 99%

Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy

et al. 2020

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“…R-848 is an agonist that binds to toll-like receptor 7/8 and has an inhibitory effect on Th2-type immunity via initiating the Th1-type immune response [30]. As allergies are related to a Th2 cell-driven immune response, R-848 is beneficial for the alleviation of allergic symptoms including allergic rhinitis [31], asthma [22], and inflammation [32]. Additionally, unlike the occlusive patch system, the S/O system is able to efficiently deliver lyophilic compounds through the SC due to the oil-vehicle.…”

Section: Discussionmentioning

confidence: 99%

A Solid-in-Oil Nanodispersion System for Transcutaneous Immunotherapy of Cow’s Milk Allergies

et al. 2020

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An allergy to cow’s milk proteins is the most common food allergy in infants and toddlers. Conventional oral immunotherapy for cow’s milk allergies requires hospital admission due to the risk of severe allergic reactions, including anaphylaxis. Therefore, a simpler and safer immunotherapeutic method is desirable. We examined transcutaneous immunotherapy with a solid-in-oil (S/O) system. In the S/O system, nano-sized particles of proteins are dispersed in an oil-vehicle with the assistance of nonionic surfactants. In the present study, the S/O system enhanced the skin permeation of the allergen molecule β-lactoglobulin (BLG), as compared with a control PBS solution. The patches containing BLG in the S/O nanodispersion skewed the immune response in the allergy model mice toward T helper type 1 immunity, indicating the amelioration of allergic symptoms. This effect was more pronounced when the immunomodulator resiquimod (R-848) was included in the S/O system.

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“…Th17 cells are a new T‐cell subset that functions in promoting inflammation and autoimmune diseases. It has been reported that upregulation of Th17 cells increases the risk of AR . Th17 cells mainly secrete IL‐17, an important effector cytokine, which promotes the production of chemokines and causes local inflammation responses .…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells combined with traditional Chinese medicine (qi‐fang‐bi‐min‐tang) alleviates rodent allergic rhinitis

Kong

et al. 2019

J of Cellular Biochemistry

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Mesenchymal stem cells (MSCs) have been proved to exert anti‐inflammatory effects and regulate immune reactions. Traditional Chinese medicine (TCM), qi‐fang‐bi‐min‐tang, is effective for some patients with allergic diseases. However, it remains unclear whether MSCs combined with TCM could benefit the treatment of allergic rhinitis (AR). In this study, we reported an additional effect of TCM (qi‐fang‐bi‐min‐tang) on the therapy of AR under MSCs treatment. Intriguingly, we observed that TCM‐treated MSCs significantly inhibited the symptoms of AR and reduced the pathological changes of nasal mucosa in ovalbumin (OVA)‐induced rats. The expression levels of interferon γ (IFN‐γ), interleukin‐17 (IL‐17), and IL‐4 were significantly decreased in the plasma of AR rats after injection of TCM‐treated MSCs. TCM‐treated MSCs reduced the levels of histamine secreted by mast cells and immunoglobulin E (IgE) secreted by plasma cells. In addition, we found that MSCs combined with TCM had a better therapeutic effect than TCM alone on AR in an OVA‐induced mouse model. After OVA induction, MSCs combined with TCM significantly reduced the ratio of T helper type 1 (Th1), Th2, and Th17, but increased the proportion of Treg in the spleen of mice. Consistently, the expression levels of IFN‐γ, IL‐4, and IL‐17 were significantly decreased, but transforming growth factor‐β1 was significantly increased in the plasma of AR mice after treated with TCM and MSCs. Our results from both rats and mice indicated that the effects of TCM combined with MSCs on the AR might be through regulating the secretion of Th1, Th2, and Th17 cytokines. This study suggested that TCM (qi‐fang‐bi‐min‐tang)‐treated MSCs could be used in the clinical therapy of AR.

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The effects of resiquimod in an ovalbumin-induced allergic rhinitis model

Cited by 9 publications

References 43 publications

Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy

Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy

A Solid-in-Oil Nanodispersion System for Transcutaneous Immunotherapy of Cow’s Milk Allergies

Mesenchymal stem cells combined with traditional Chinese medicine (qi‐fang‐bi‐min‐tang) alleviates rodent allergic rhinitis

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