ALLERGY
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2021
·Vol. 77
·期 2
·483-498
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IF 13.146
Renlan Wu,Xiefang Yuan,Xingjie Li,Ning Ma,Hongyu Jiang,Hongmei Tang,Guofeng Xu,Zhigang Liu,Zongde Zhang
Background Alteration of commensal microbiota is highly correlated with the prevalence of allergic reactions to food in the gastrointestinal tract. The mechanisms by which microbiota modulate food allergen sensitization in the mucosal site are not fully understood. Methods We generate DCs specific knockout of retinoic acid receptor α (Rara) gene mice (DC KO Rara) to evaluate food sensitization. The bile acid-activated retinoic acid response was evaluated by flow cytometry, real-time RT-PCR and Illumina transcriptome sequencing. The global effect of Abx treatment on BA profiles in the mucosal lymph tissue mLN in mice was examined by UPLC-MS analysis. Results In this study, we demonstrate that depletion of commensal gut bacteria leads to enhanced retinoic acid (RA) signaling in mucosal dendritic cells (DCs). RA signaling in DCs is required for the production of food allergen-specific IgE and IgG1. Antibiotics induced an enlarged bile acid (BA) pool, and dysregulated BA profiles contributed to enhanced RA signaling in mucosal DCs. BA-activated RA signaling promoted DC upregulation of interferon I signature, RA signature, OX40L, and PDL2, which may lead to T helper 2 differentiation of CD4+ T cells. BA-activated RA signaling involved the farnesoid X receptor and RA receptor α (RARa) interaction. Depletion of bile acid reduces food allergen specific IgE and IgG1 levels in mice. Conclusion Our research unveils a mechanism of food sensitization modulated by BA-RA signaling in DCs, which suggests a potential new approach for the intervention of food allergic reactions.
研究领域:
免疫学
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微生物学
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过敏
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分子生物学
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DOI
PubMed
高影响因子
Jove-Journal of Visualized Experiments
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2023
·
IF 1.2
Xiaoqiang Zeng,Hongwu Sun,Yan Ye,Xing Luo,Dingyi Cai,Yun Yang,Ting Chen,Cun Sun,Shaotong Zhang,Hao Zeng
Nanoemulsion adjuvant vaccines have attracted extensive attention because of their small particle size, high thermal stability, and ability to induce validly immune responses. However, establishing a series of comprehensive protocols to evaluate the immune response of a novel nanoemulsion adjuvant vaccine is vital. Therefore, this article features a rigorous procedure to determine the physicochemical characteristics of a vaccine (by transmission electron microscopy [TEM], atomic force microscopy [AFM], and dynamic light scattering [DLS]), the stability of the vaccine antigen and system (by a high-speed centrifuge test, a thermodynamic stability test, SDS-PAGE, and western blot), and the specific immune response (IgG1, IgG2a, and IgG2b). Using this approach, researchers can evaluate accurately the protective effect of a novel nanoemulsion adjuvant vaccine in a lethal MRSA252 mouse model. With these protocols, the most promising nanoemulsion vaccine adjuvant in terms of effective adjuvant potential can be identified. In addition, the methods can help optimize novel vaccines for future development.
研究领域:
疫苗学
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免疫学
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微生物学
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药学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Zhuwei Liang,Chao Zhang,Xiaoyu Liu,Kaiyue Yang,Zhile Xiong,Bingshao Liang,Jialiang Mai,Xiaojun Xiao,Jie Liu,Pingchang Yang,Damo Xu,Zhenwen Zhou
Background: Milk allergy commonly occurs in children, mainly caused by bovine-derived casein (CAS) protein. Neutrophil-activating protein (NAP) of Helicobacter pylori plays an immunomodulatory role with potential to suppress Th2-type immune responses. Bacillus subtilis (B. subtilis) spores are commonly used as oral vectors for drug delivery.Objective: To investigate whether recombinantly expressed NAP on B. subtilis spores could be an effective treatment for CAS allergy in mouse.Methods: After CAS sensitization, mice were orally administered B. subtilis spores expressing recombinant NAP for 6 weeks. Allergic symptoms and parameters were evaluated after CAS challenge oral gavage, including allergic inflammation, splenic cytokines, and serum-specific antibodies. Protein levels of Toll-like receptor 2 (TLR2) and c-JUN in the jejunum tissue were measured by western blot. Bone marrow-derived macrophages (BMDMs) were stimulated with inactivated NAP spores to measure the influence on cytokine profiles in vitro.Results: NAP recombinant spore treatment significantly reduced allergic symptoms and intestinal inflammation. Interleukin-12 and interferon-gamma levels increased, whereas serum CAS-specific IgG1 and IgE levels decreased. TLR2 and c-JUN expression levels were elevated in the jejunal tissue. Inactivated NAP spores polarized BMDMs to the M1 phenotype and enhanced cytokine expression, which were inhibited by a TLR2 neutralizing antibody.Conclusion: NAP offers a new strategy in the treatment of CAS allergy by inhibiting the Th2 response, while eliciting macrophages to promote Th1 immune responses.
研究领域:
免疫学
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过敏
·
微生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDIATORS OF INFLAMMATION
·
2022
·
IF 4.529
Hao Xiong,Jin Yang,Tao Liu,Guangren Liu,Yongzhi Han,Xiuqin Dong
Atopic dermatitis (AD) is a chronic skin inflammatory disease associated with immune abnormalities and disrupted skin barrier function. Mesenchymal stem cells (MSCs) have been suggested as an alternative therapeutic option in AD. Stem cells from human exfoliated deciduous teeth (SHEDs) are a unique postnatal stem cell population with high immunomodulatory properties. The aim of this study was to explore the effects of SHEDs on AD in the BALB/c mouse model induced by 2,4-dinitrochlorobenzene (DNCB). SHEDs were administrated intravenously or subcutaneously, and clinical severity, histopathological findings, skin barrier function, and organ indexes were evaluated. Skin tissue cytokine mRNA levels and serum cytokine protein levels were further analysed. SHED administration significantly alleviated AD clinical severity, including dermatitis scores, ear thickness, scratching behaviour, and infiltration of mast cells. In addition, disrupted skin barrier function and enlarged spleens were restored by SHED administration. Further, SHED treatment reduced the levels of IgE, IgG1, and thymic stromal lymphopoietin (TSLP) in the serum and the modulated expression of Th1-, Th2-, and Th17-associated cytokines in skin lesions. In conclusion, SHEDs attenuated AD-like skin lesions in mice by modulating the immune balance and skin barrier function. SHEDs could be a potential new treatment agent for AD.
研究领域:
免疫学
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皮肤病学
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干细胞研究
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炎症性疾病
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DOI
PubMed
高影响因子
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