The role of the IL-23/Th17 axis as modulator of B cell-mediated (auto)immune responses

我们之前发表的数据表明，IL-23/Th17轴作为B细胞介导的免疫球蛋白G(Ig G)糖基化、Ig G活性和浆母细胞扩张的调节器起着关键作用。其他初步数据显示，在B细胞激活和自身免疫性疾病期间，B细胞上IL-17受体(R)、IL-22R和GMCSFR的表达和调节存在差异。总之，这些数据表明，Th17衍生的信号直接或间接地影响B细胞和浆细胞反应的关键步骤，尽管潜在的机制和后果仍然难以捉摸。因此，在拟议的项目中，我们计划扩大我们的分析范围，并解决IL-23/Th17轴对B细胞生物学和B细胞介导的自身免疫性疾病的全球影响。特别是，我们的目标是进一步确定相关的细胞因子，并描述介导Th17细胞/B细胞串扰的潜在分子机制，以确定治疗自身免疫性和慢性炎症性疾病的新靶点。

Our previously published data point towards a key role of the IL-23/Th17 axis as modulator of B cell-mediated Immunoglobulin G (IgG) glycosylation, IgG activity and plasmablast expansion. Additional preliminary data show a differential expression and regulation of the IL-17 Receptor (R), IL-22R and GMCSFR on B cells during B cell activation and during autoimmune disease. Together these data suggest that Th17-derived signals directly or indirectly affect key steps of the B cell and plasma cell response, although underlying mechanisms and consequences remain elusive. In the proposed project we therefore plan to expand our analyses and to address the global impact of the IL-23/Th17 axis on B cell biology and B cell-mediated autoimmune diseases. In particular, we aim to further identify involved cytokines and delineate underlying molecular mechanisms that mediate Th17 cell/B cell crosstalk in order to determine novel targets for the therapy of autoimmune and chronic inflammatory diseases.