Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis

Suzuki, Motohiko; Yokota, Makoto; Nakamura, Yoshihisa; Ozaki, Shinya; Murakami, Shingo

doi:10.1016/j.alit.2016.08.014

Cited by 33 publications

(37 citation statements)

References 35 publications

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“…Eosinophils were counted at 6 randomly selected locations in the anterior, middle, and posterior areas on the right and left sides of each mouse. The 6 counts were averaged for each mouse, and results are expressed as means ± SEM of 5 mice, as previously reported [4][5][6]17]. The observer who counted the number of eosinophils was blinded to the treatment.…”

Section: Pathologymentioning

confidence: 99%

Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

Suzuki

Yokota

Matsumoto

et al. 2018

Int Arch Allergy Immunol

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Background: We previously reported that siRNA-induced CD40-silenced dendritic cells (DCs) inhibit allergic responses and symptoms. However, more potent therapies are needed. To our knowledge, synergic effects of gene silencing in DCs by ≥2 siRNAs have not been reported to control allergic diseases. Therefore, we investigated the synergistic effects of the silencing of CD40 and CD86 in DCs on allergic responses. Methods: Mice were treated with CD40/CD86-silenced DCs, which were transfected with CD40/CD86 siRNAs and pulsed with ovalbumin (OVA) antigen. The effects of these DCs on allergic symptoms and allergic responses were estimated. Results: The administration of CD40/CD86-silenced OVA-pulsed DCs significantly inhibited the number of sneezes and nasal rubbing movements, the number of eosinophils in the nasal mucosa, and the level of OVA-specific IgE when compared with those for CD40- or CD86-silenced OVA-pulsed DCs alone (p < 0.01). These inhibitory effects were detected before sensitization as well as after the establishment of allergic rhinitis. CD40/CD86-silenced OVA-pulsed DCs did not inhibit KLH-induced allergies. Foxp3 gene expression was significantly upregulated in CD40-silenced DCs compared to in CD86-silenced DCs (p < 0.01). IL-4 production by T cells was suppressed more substantially when using CD86-silenced DCs than with CD40-silenced DCs (p < 0.01). Conclusions: These results indicate, for the first time, that siRNA-induced CD40/CD86-silenced antigen-specific DCs have greater inhibitory effects against allergic responses than those of CD40- or CD86-silenced antigen-specific DCs alone. This study also suggests that the synergic effects of gene silencing in DCs by ≥2 siRNAs are useful for the control of allergic diseases. Thus, owing to the synergistic effects, CD40 and CD86 silencing has the potential to substantially improve the treatment of allergic diseases.

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Section: Pathologymentioning

confidence: 99%

Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

Suzuki

Yokota

Matsumoto

et al. 2018

Int Arch Allergy Immunol

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“…The number of eosinophils was counted in 6 randomly selected locations in the anterior, middle, and posterior areas on the right and left side for each mouse. The 6 counts were averaged for each mouse, as previously reported [6-9]. The observer who counted the number of eosinophils was unaware of which treatment the sample received.…”

Section: Methodsmentioning

confidence: 99%

“…Cells were cultured for 3 days and pulsed with 1 µCi [ 3 H]thymidine. Incorporated radioactivity was quantitated using a liquid scintillation counter [6-9]. Results are presented as mean counts per minute of triplicate cultures ± standard error of the mean.…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was isolated from T cells using TRIzol, and real-time PCR was performed as described previously [6-9]. The primers for Foxp3 were as follows: sense 5′CAGCTGCCTACAGTGCCCCTAG-3′ and antisense 5′-CATTTGCCAGCAGTGGGTAGCTG-3′.…”

Section: Methodsmentioning

confidence: 99%

“…Sneezes and nasal rubbing movements were counted for 20 min immediately after the last nasal challenge, according to the previously described method [6-9]. …”

Section: Methodsmentioning

confidence: 99%

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Intranasal Administration of IL-27 Ameliorates Nasal Allergic Responses and Symptoms

Suzuki

Yokota

Ozaki

et al. 2018

Int Arch Allergy Immunol

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Background: Interleukin 27 (IL-27) is an initiator of the Th1 response and inhibits inflammatory responses. In a mouse model of asthma, administration of IL-27 reduced eosinophil numbers in bronchoalveolar lavage fluid and airway hyperresponsiveness. However, it is unclear whether administration of IL-27 can inhibit symptoms of allergic diseases and allergic rhinitis as a therapeutic agent. Therefore, we investigated the in vivo effect of IL-27 on nasal symptoms and allergic rhinitis. Methods: Mice sensitized and challenged with ovalbumin (OVA) antigen received intranasal administration of IL-27. Results: Intranasal administration of IL-27 significantly suppressed the number of sneezes and nasal rubbing movements, the number of eosinophils, OVA-specific T-cell responses in cervical lymph nodes, production of IL-4 and IL-5, and OVA-specific IgE in sera, compared with the administration of PBS alone. The production of IL-10 and IL-35, the percentage of CD25+Foxp3+ cells, and the gene expression of Foxp3 in mice that received intranasal administration of IL-27 were also significantly higher than those in mice that received only PBS. Conclusions: This study showed, for the first time, that intranasal administration of IL-27 inhibited nasal allergic responses and symptoms even after the establishment of allergic rhinitis and suggested that IL-27 is useful as an intranasal therapeutic agent.

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Regulatory B cells induced by interleukin‐35 inhibit inflammation and alveolar bone resorption in ligature‐induced periodontitis

Liu

et al. 2023

Journal of Periodontology

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BackgroundRegulatory B cells (Bregs) have been reported to suppress immune responses and alveolar bone loss in murine periodontitis models. These cells could be induced by interleukin (IL)‐35 which is increased upon periodontal inflammation. Thus, this study aimed to explore the role of Bregs induced by IL‐35 in periodontitis.MethodsExperimental periodontitis was induced in mice by ligature. Two weeks after ligation, the test group was systemically treated with IL‐35 for 1 week. Four weeks after ligation, all mice were euthanized, and alveolar bone loss was evaluated by microcomputed tomography. Cytokines associated with periodontitis were analyzed using reverse transcription‐quantitative polymerase chain reaction and enzyme‐linked immunosorbent assay. Bregs in spleens, cervical lymph nodes, and periodontal tissues were detected by flow cytometry and immunofluorescence staining.ResultsIn the mouse model of periodontitis, IL‐35 induced the expansion of CD1dhiCD5+ B10 cells with increased interleukin‐10 (IL‐10) and IL‐35 production. IL‐35 administration also attenuated alveolar bone loss and reduced the levels of proinflammatory cytokines in situ.ConclusionsFollowing ligature‐induced periodontitis in mice, IL‐35 inhibited periodontal inflammation and alveolar bone resorption at least partially through the induction of B10 cells and IL‐35+ Bregs.

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Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis

Abstract: This study showed for the first time that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL-35 increases IL-10, Foxp3, and CD4CD25 regulatory T cells in CLN. This study also suggests that intranasal administration of IL-35 can attenuate allergic rhinitis.

Cited by 33 publications

References 35 publications

Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

Intranasal Administration of IL-27 Ameliorates Nasal Allergic Responses and Symptoms

Regulatory B cells induced by interleukin‐35 inhibit inflammation and alveolar bone resorption in ligature‐induced periodontitis

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