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.
The proposed research will provide a greater understanding of the effects of IL-17A on mucosal and systemic IgA responses. The studies in this proposal will impact several areas relevant to human health, such as oral vaccines, autoimmunity, inflammatory bowel disease, and long-lived antibody- mediated immunity.
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