PDF(Pubmed)
Abstract：
BACKGROUND: The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund\'s adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll-like receptor (TLR) ligands as compared to CFA.
METHODS: A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein-3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme-linked immunosorbent assay quantified antigen-specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes.
RESULTS: TLR ligands demonstrated efficacy in inducing PV-like symptoms in wild-type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self-antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study.
CONCLUSIONS: The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis.
UNASSIGNED: Immunization with desmoglein 3 and Toll-like receptor (TLR) ligands effectively induces pemphigus symptoms in wild-type mice, whereas complete Freund\'s adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10, leading to more effective immune responses.
METHODS: A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein-3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme-linked immunosorbent assay quantified antigen-specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes.
RESULTS: TLR ligands demonstrated efficacy in inducing PV-like symptoms in wild-type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self-antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study.
CONCLUSIONS: The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis.
UNASSIGNED: Immunization with desmoglein 3 and Toll-like receptor (TLR) ligands effectively induces pemphigus symptoms in wild-type mice, whereas complete Freund\'s adjuvant (CFA) fails. TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model. CFA promoted regulatory T cells and IL-10-producing neutrophils, whereas TLR ligands downregulated CCL17 and IL-10, leading to more effective immune responses.
摘要：
背景：精心选择合适的疫苗佐剂对于优化免疫反应至关重要。传统上,寻常型天疱疮（PV），一种自身免疫性疾病，已使用完全弗氏佐剂(CFA)建模。在这项研究中,我们的目的是辨别与CFA相比,Toll样受体(TLR)配体引起的免疫反应的潜在变化.
方法：进行了全面调查，比较这些佐剂与卵清蛋白或桥粒糖蛋白-3的联合作用。流式细胞术用于分析不同的细胞亚群，而酶联免疫吸附试验定量抗原特异性抗体和细胞因子水平。进行收获的皮肤组织的组织学检查和皮肤损伤的转录组分析以鉴定差异表达的基因。
结果：TLR配体显示出在野生型小鼠中诱导PV样症状的功效，与CFA相反。这强调了佐剂对自身抗原耐受性的实质性影响。此外，我们提出了一种通过过继转移建立光伏模型的增强方法，用TLR配体取代CFA。我们的结果表明，与CFA是最有效的免疫增强剂的观点相反，CFA促进调节性T细胞（Treg），滤泡调节性T细胞和产生IL-10的中性粒细胞，而TLR配体下调CCL17和IL-10。这表明对Treg亚群的募集和激活的潜在影响。虽然B细胞和CD8+T细胞反应表现出相似性，CFA在树突状细胞亚群中诱导较少的活化。本研究提供了一种新型PV小鼠模型和佐剂免疫刺激作用的系统比较。
结论：CFA和TLR配体的系统比较揭示了这些佐剂的独特性质，为天疱疮的研究提供创新的小鼠模型。这项研究为辅助研究做出了重要贡献，并促进了我们对PV发病机理的理解。
■用桥粒蛋白3和Toll样受体（TLR）配体免疫可有效诱导野生型小鼠天疱疮症状，而完全弗氏佐剂（CFA）失败。TLR配体在过继转移天疱疮模型中提高了供体细胞的自身反应性。CFA促进调节性T细胞和产生IL-10的中性粒细胞，而TLR配体下调CCL17和IL-10，导致更有效的免疫反应。
方法：进行了全面调查，比较这些佐剂与卵清蛋白或桥粒糖蛋白-3的联合作用。流式细胞术用于分析不同的细胞亚群，而酶联免疫吸附试验定量抗原特异性抗体和细胞因子水平。进行收获的皮肤组织的组织学检查和皮肤损伤的转录组分析以鉴定差异表达的基因。
结果：TLR配体显示出在野生型小鼠中诱导PV样症状的功效，与CFA相反。这强调了佐剂对自身抗原耐受性的实质性影响。此外，我们提出了一种通过过继转移建立光伏模型的增强方法，用TLR配体取代CFA。我们的结果表明，与CFA是最有效的免疫增强剂的观点相反，CFA促进调节性T细胞（Treg），滤泡调节性T细胞和产生IL-10的中性粒细胞，而TLR配体下调CCL17和IL-10。这表明对Treg亚群的募集和激活的潜在影响。虽然B细胞和CD8+T细胞反应表现出相似性，CFA在树突状细胞亚群中诱导较少的活化。本研究提供了一种新型PV小鼠模型和佐剂免疫刺激作用的系统比较。
结论：CFA和TLR配体的系统比较揭示了这些佐剂的独特性质，为天疱疮的研究提供创新的小鼠模型。这项研究为辅助研究做出了重要贡献，并促进了我们对PV发病机理的理解。
■用桥粒蛋白3和Toll样受体（TLR）配体免疫可有效诱导野生型小鼠天疱疮症状，而完全弗氏佐剂（CFA）失败。TLR配体在过继转移天疱疮模型中提高了供体细胞的自身反应性。CFA促进调节性T细胞和产生IL-10的中性粒细胞，而TLR配体下调CCL17和IL-10，导致更有效的免疫反应。
