Mechanisms of systemic IgA induction by commensal bacteria

 描述(申请人提供)：免疫球蛋白是粘膜屏障表面的关键成分，但对其系统诱导和维持知之甚少。这个建议的主要目的是为了更好地了解全身免疫球蛋白A诱导的机制和共生细菌诱导的细胞因子IL-17A的作用。我们的初步数据表明，IL-17A是免疫球蛋白A浆细胞在骨髓中定植的关键因素。IL-17A与自身免疫性疾病有关，并在中性粒细胞趋化中发挥作用，但目前对IL-17A在IgA应答中的作用知之甚少。这些实验将通过以下工作阐明IL-17A在IgA中的作用：1)确定IL-17A诱导系统IgA的机制；2)确定IL-17A在局部和系统对沙门氏菌感染的IgA反应中的作用。这些研究将增强我们对粘膜和系统抗体介导的免疫和影响领域的知识，如口服疫苗开发、自身免疫和炎症性肠病。

 DESCRIPTION (provided by applicant): IgA is a critical component of mucosal barrier surfaces, but little is known about its systemic induction and maintenance. The main goals of this proposal are to better understand the mechanisms of systemic IgA induction and the role of the commensal bacteria induced cytokine IL-17A. Our preliminary data suggest that IL-17A is a critical factor in the colonization of the bone marrow with IgA plasma cells. IL-17A has been implicated in autoimmune disease and plays a role in neutrophil chemotaxis, but currently there is little known about the role of IL-17A in IgA responses. The proposed experiments will shed light on the role of IL-17A in IgA by doing the following: 1) Determine the mechanism of systemic IgA induction by IL-17A and 2) Define the role of IL-17A in local and systemic IgA responses to Salmonella infection. These studies will enhance our knowledge of mucosal and systemic antibody-mediated immunity and impact areas, such as oral vaccine development, autoimmunity, and inflammatory bowel disease.