Mechanisms of systemic IgA induction by commensal bacteria

 描述（由申请人提供）：伊加是粘膜屏障表面的关键组分，但对其全身诱导和维持知之甚少。该提案的主要目标是更好地理解全身性伊加诱导的机制和肠道细菌诱导的细胞因子IL-17 A的作用。我们的初步数据表明，IL-17 A是一个关键因素，在骨髓中的伊加浆细胞的殖民。IL-17 A与自身免疫性疾病有关，并在中性粒细胞趋化性中发挥作用，但目前对IL-17 A在伊加应答中的作用知之甚少。所提出的实验将通过以下方式阐明IL-17 A在伊加中的作用：1）确定IL-17 A诱导全身伊加的机制和2）确定IL-17 A在沙门氏菌感染的局部和全身伊加应答中的作用。这些研究将增强我们对粘膜和全身抗体介导的免疫和影响领域的认识，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.