Suppression of Allergic Diarrhea in Murine Ovalbumin-Induced Allergic Diarrhea Model by PG102, a Water-Soluble Extract Prepared from &lt;i&gt;Actinidia arguta&lt;/i&gt;

Kim, Dong-Hyun; Kim, Seon Hee; Park, Eun Jin; Kim, Jiyoung; Cho, Sang Heon; Kagawa, Junko; Arai, Naoko; Kunisawa, Jun; Kiyono, Hiroshi; Kim, Sun‐Young

doi:10.1159/000218119

Cited by 20 publications

(15 citation statements)

References 46 publications

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“…Splenocytes were isolated from spleen on day 14 after a single immunization as described 49 . Briefly, spleens were mashed through a cell strainer (Falcon) and then the cells were spun down and resuspended in RBC lysis buffer (eBioscience).…”

Section: Methodsmentioning

confidence: 99%

Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin

Kim

Seo

et al. 2016

Nat Med

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104

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Cholera toxin (CT) is a potent adjuvant for inducing mucosal immune responses. However, the mechanism by which CT induces adjuvant activity remains unclear. Here we show that the microbiota is critical for inducing antigen-specific IgG production after intranasal immunization. After mucosal vaccination with CT, both antibiotic-treated mice and germ-free (GF) had reduced antigen-specific IgG, recall-stimulated cytokine responses, an impaired follicular helper T (TFH) response and reduced plasma cells. Recognition of symbiotic bacteria via Nod2 in CD11c+ cells was required for the adjuvanticity of CT. Reconstitution of GF mice with a Nod2 agonist or Staphylococcus sciuri having high Nod2-stimulatory activity was sufficient to promote robust CT adjuvant activity whereas bacteria with low Nod2-stimulatory activity did not. Mechanistically, CT enhanced Nod2-mediated cytokine production in DCs via intracellular cAMP. These results show an important role for the microbiota and the intracellular receptor Nod2 in promoting the mucosal adjuvant activity of CT.

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Section: Methodsmentioning

confidence: 99%

Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin

Kim

Seo

et al. 2016

Nat Med

Self Cite

104

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“…Splenocytes were isolated from spleens on day 14 after immunization as previously described . Briefly, spleens were mashed through a cell strainer (Falcon, Thermo Fisher Scientific, Waltham, MA), and then the cells were spun down and resuspended in red blood cell lysis buffer (eBioscience, San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin‐1β

Kim

et al. 2019

Immunology

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The role of symbiotic bacteria in the development of antigen-specific immunity remains poorly understood. Previous studies showed that sensing of symbiotic bacteria by nucleotide-binding oligomerization domaincontaining protein 2 (Nod2) regulates antibody responses in response to nasal immunization with antigen and cholera toxin (CT). In this study, we examined the role of the microbiota in the adjuvant activity of CT induced after oral immunization with antigen. Germ-free (GF) mice showed impaired production of antibody responses and T-cell-specific cytokines after oral immunization when compared with that observed in conventionally raised mice. Similar to GF mice, Nod2-deficient mice showed reduced humoral responses upon oral immunization with antigen and CT. Treatment with CT enhanced the production of interleukin-1b (IL-1b), but not tumor necrosis factor-a or IL-12p40, induced by stimulation of dendritic cells with muramyl dipeptide, the Nod2 ligand. Mechanistically, the enhanced production of IL-1b induced by muramyl dipeptide and CT stimulation required Nod2 and was mediated by both increased synthesis of pro-IL-1b and caspase-1 activation. Furthermore, antigen-specific antibody and cytokine responses induced by CT were impaired in orally immunized IL-1b-deficient mice. Collectively, our results indicate that Nod2 stimulation by symbiotic bacteria contributes to optimal CT-mediated antigen-specific oral vaccination through the induction of IL-1b production.

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“…Although the avoidance of foods that cause allergies can be effective, accidental ingestion through cross‐contamination remains a problem (Kim and others ). In addition, allergy treatment drugs, such as corticosteroids often cause side effects (Popescu ).…”

Section: Discussionmentioning

confidence: 99%

Citrus Tachibana Leaf Extract Mitigates Symptoms of Food Allergy by Inhibiting Th2‐Associated Responses

Chung

Shin

Choi

et al. 2016

Journal of Food Science

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Although the incidence of food allergy continues to rise, there have been no effective therapeutic strategies. Citrus fruits contain a number of bioactive flavonoids with immune-regulatory functions. The objective of this study was to determine whether Citrus tachibana (fruit body with peel, leaves, and branch) can protect against the development of food allergy and the mechanism behind it, and to identify the active compound(s) responsible. We found that C. tachibana leaf extract (CLE) mitigated ovalbumin (OVA)-induced food allergy symptoms including increased rectal temperature, diarrhea, and anaphylaxis. This mitigation was likely due to CLE-mediated decreases in cytokine release from T-helper 2 cells (Th2 cells) in mesenteric lymph nodes. Moreover, higher levels of CLE attenuated systemic Th2 cell-mediated responses in mouse splenocytes sensitized with OVA+Alum. This was evidenced by CLE-mediated reductions in Th2 cytokine release, including interleukin (IL)-4, IL-5, and IL-13, but not the Th1 cytokines IL-12 and interferon (IFN)-γ, which was attributable to decreased gene expression levels. We also identified kaempferol as the most potent compound for reducing Th2-associated responses in splenocytes. The findings of this study suggest that CLE suppresses Th2-cell-mediated immune responses, contributing to alleviation of food allergy symptoms, and that kaempferol is a flavonoid with potential antiallergenic activity that targets Th2 cell-induced responses.

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Suppression of Allergic Diarrhea in Murine Ovalbumin-Induced Allergic Diarrhea Model by PG102, a Water-Soluble Extract Prepared from <i>Actinidia arguta</i>

Cited by 20 publications

References 46 publications

Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin

Nod2-mediated recognition of the microbiota is critical for mucosal adjuvant activity of cholera toxin

Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin‐1β

Citrus Tachibana Leaf Extract Mitigates Symptoms of Food Allergy by Inhibiting Th2‐Associated Responses

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