Intranasal administration of CpG oligodeoxynucleotides reduces lower airway inflammation in a murine model of combined allergic rhinitis and asthma syndrome

Li, Hongtao; Zhang, Tiantuo; Chen, Zhuang‐Gui; Ye, Jin; Liu, Hui; Zou, Xiaoling; Wang, Yanhong; Yang, Hailing

doi:10.1016/j.intimp.2015.06.028

Cited by 20 publications

(5 citation statements)

References 43 publications

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“…When administered post-allergen sensitisation via the intranasal route, promising results were also observed with reduced eosinophil infiltration, IL-4 and IL-5 levels, serum levels of OVA-specific IgE and symptom scores ( 158 ). When administered via the intradermal route, this was not observed ( 159 ). As highlighted previously in humans, anti-allergic effects of CpG ODN were mediated through IL-12 promoted IFN-γ production ( 103 ).…”

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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“…In addition, allergic rhinitis and asthma often co-exist in what is known as combined allergic rhinitis and asthma syndrome (CARAS), thus emphasizing the inter relationship between the lower and upper airways [45]. In a study involving a CARAS model, BALB/c mice were sensitized to OVA intraperitoneally and subsequently challenged with CpG-ODN and OVA intranasally which was followed by OVA aerosol exposure (lower airway) in an attempt to establish that delivery of CpG-ODN to the upper airway could affect lower airway inflammation [46]. It was found that upper airway treatment of CARAS mice with soluble CpG-ODN significantly reduced the symptoms of allergic rhinitis, lower airway inflammation and AHR.…”

Section: Immunostimulatory Effects Of Soluble Cpg-odn In Allergic Asthmamentioning

confidence: 99%

“…Intradermal administration of soluble CpG-ODN, on the other hand, was ineffective. The same group subsequently investigated the mechanism by which CpG-ODN may have mediated its effects in the CARAS mice and concluded that CpG-ODN may potentially suppress the activity of TSLP, an epithelial/fibroblastic-derived protein that is known to promote pulmonary Th2 responses to allergen [46,47]. Allergies caused by Japanese cedar pollen (JCP) affect approximately 10% of the Japanese population annually, and is therefore an important model for consideration in allergic asthma treatment.…”

Section: Immunostimulatory Effects Of Soluble Cpg-odn In Allergic Asthmamentioning

confidence: 99%

Nanoparticle-Based Cpg-Oligonucleotide Therapy For Treating Allergic Asthma

2018

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Allergic asthma is becoming increasingly prevalent in the developed world, and many common allergens are capable of inducing allergic asthma responses, particularly in atopic individuals. Unmethylated CpG-oligonucleotide (ODN) therapy can shift the immune response to mitigate these allergic responses. Therapeutic and prophylactic delivery of soluble CpG-ODN in preclinical studies has shown promise in treating existing asthma and preventing allergic responses upon subsequent allergen exposure, respectively. However, when CpG-ODN is coupled with nanoparticles or self assembled into nanostructures, improved efficacy of CpG-ODN treatment for several common allergens is observed in preclinical studies and clinical trials. Here we discuss the role of CpG-ODN in treating allergic asthma and how nanoparticle-based delivery can further enhance its therapeutic properties.

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“…CARAS is a new medical concept proposed in recent years [17], and two symptoms of allergic rhinitis and asthma are similar in pathogenesis, genetic changes, local pathological changes, immune function and pathogenesis [3,18]. 40% of allergic rhinitis cases are concomitant with asthma while up to 80% of asthma patients are affected by allergic rhinitis [19][20][21].…”

Section: Discussionmentioning

confidence: 99%

MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation

Zhiguang Liu,

Chuang Sun,

Yujia Shi

et al. 2024

Cell Mol Biol (Noisy-le-grand)

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Abnormal expression of non-coding microRNA is associated with the development of combined allergic rhinitis and asthma syndrome (CARAS). However, the function of miR-4454 in CARAS is unknown. Our study aimed to reveal the clinical significance and related mechanism of miR-4454 in CARAS. Blood samples from 38 cases of CARAS and 43 cases of healthy subjects were collected to detect the expression of miR-4454. House dust mite (HDM) sensitization and challenge-induced bronchial epithelial cells to simulate the asthma state model in vitro, miR-4454 mimics and inhibitor transfection to detect the expression level of pro-inflammatory cytokines, cell survival rate and migration ability, flow cytometry and western blot (WB) Detection of cell cycle, apoptosis and inflammation-related protein levels. Compared with healthy controls, the expression of miR-4454 in the blood of CARAS patients was significantly up-regulated, and IL-6 and IL-8 were significantly up-regulated in the HDM treatment group, indicating that the model induction was successful. After overexpression of miR-4454, cell proliferation and migration in the HDM-treated group were significantly inhibited, and the levels of early apoptosis and inflammation-related proteins (IL-17, IL-17RD, TNF-α, GCSF and NF-κB) were increased High; after inhibiting miR-4454, cell proliferation and migration were significantly enhanced, and the levels of apoptosis and inflammation-related proteins were decreased. This study found that inhibiting the expression of miR-4454 can improve HDM-induced cell injury, which may be related to miR-4454 regulating the activation of IL-17/NF-кB inflammatory axis.

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Intranasal administration of CpG oligodeoxynucleotides reduces lower airway inflammation in a murine model of combined allergic rhinitis and asthma syndrome

Cited by 20 publications

References 43 publications

Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy

Toll-Like Receptor Agonists as Adjuvants for Allergen Immunotherapy

Nanoparticle-Based Cpg-Oligonucleotide Therapy For Treating Allergic Asthma

MiR-4454 in Combined Allergic Rhinitis and Asthma Syndrome (CARAS): Clinical significance and mechanistic insights into airway inflammation

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