TLR2 activation underlying immune regulation at interfaces

TLR2 激活是界面免疫调节的基础

• 批准号: 212173602
• 负责人: Professor Dr. Tilo Biedermann
• 金额: --
• 依托单位: Klinik und Poliklinik für Dermatologie und Allergologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/212173602?language=en
• 关键词: TLR2; activation; underlying; immune; regulation

Innate immune signals mediate pro-, anti-inflammatory and/or tolerogenic responses. We identified TLR2 activation as important pathway to induce IL 10 production, regulatory T cells and to suppress atopic dermatitis in both humans and mouse models. Functional analyses of TLR2 ligands revealed that cutaneous application of di-acylated Pam2Cys, but not of tri-acylated Pam3Cys, inhibited subsequent cutaneous inflammation, and IgE and IgG1 responses. These findings indicate that immune modulation is mediated by TLR2-TLR6 ligands (Pam2Cys) but not by TLR1-TLR2 ligands (Pam3Cys). Whether natural lipoproteins of Staphylococcus aureus are di- or tri-acylated is still controversial. We hypothesize that in pathogenic species the lipid moiety of lipoproteins is tri-acylated, because of the additional N-acylation, and in non-pathogenic (commensal) staphylococci these are only di-acylated. With our approach, we hope to find an answer to one of the central questions in immunology, why commensal bacteria on our skin are more easily tolerated by the immune system while pathogenic species readily induce inflammation.

先天免疫信号介导促炎、抗炎和/或致耐受性应答。我们在人和小鼠模型中鉴定了TLR 2活化作为诱导IL 10产生、调节性T细胞和抑制特应性皮炎的重要途径。TLR 2配体的功能分析显示，皮肤应用二酰化Pam 2Cys，但不是三酰化Pam 3Cys，抑制随后的皮肤炎症，IgE和IgG 1反应。这些发现表明免疫调节由TLR 2-TLR 6配体（Pam 2Cys）介导，而不是由TLR 1-TLR 2配体（Pam 3Cys）介导。金黄色葡萄球菌的天然脂蛋白是二酰化还是三酰化仍有争议。我们假设，在致病性物种的脂蛋白的脂质部分是三酰化的，因为额外的N-酰化，和在非致病性（葡萄球菌）葡萄球菌，这些只有二酰化。通过我们的方法，我们希望找到免疫学中一个核心问题的答案，为什么我们皮肤上的细菌更容易被免疫系统耐受，而致病物种更容易引起炎症。

项目成果

Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells.

• DOI: 10.1038/jid.2013.291
• 发表时间: 2014
• 期刊: The Journal of investigative dermatology
• 作者: T. Volz;Y. Skabytska;E. Guenova;Ko-Ming Chen;J. Frick;C. Kirschning;S. Kaesler;M. Röcken;T. Biedermann

Staphylococcus aureus-derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2.

金黄色葡萄球菌衍生的脂磷壁酸诱导暂时性 T 细胞麻痹，不依赖于 Toll 样受体 2

• DOI: 10.1016/j.jaci.2015.11.043
• 发表时间: 2016
• 期刊: The Journal of allergy and clinical immunology
• 作者: Kaesler S;Skabytska Y;Chen K;Kempf W;Volz T;Köberle M;Wölbing F;Hein U;Hartung T;Kirschning C;Röcken M;Biedermann T
• 通讯作者: Biedermann T

Staphylococcus aureus skin colonization is promoted by barrier disruption and leads to local inflammation

屏障破坏促进金黄色葡萄球菌在皮肤定植并导致局部炎症

• DOI: 10.1111/exd.12083
• 发表时间: 2014
• 期刊: Experimental Dermatology
• 影响因子: 3.6
• 作者: Wanke I;Skabytska Y;Kraft B;Peschel A;Biedermann T;Schittek B
• 通讯作者: Schittek B