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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI114089-02
Application #
9086105
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gondre-Lewis, Timothy A
Project Start
2015-07-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Wilmore, Joel R; Allman, David (2017) Here, There, and Anywhere? Arguments for and against the Physical Plasma Cell Survival Niche. J Immunol 199:839-845
Wilmore, Joel R; Jones, Derek D; Allman, David (2017) Protocol for improved resolution of plasma cell subpopulations by flow cytometry. Eur J Immunol 47:1386-1388
Jones, Derek D; Gaudette, Brian T; Wilmore, Joel R et al. (2016) mTOR has distinct functions in generating versus sustaining humoral immunity. J Clin Invest 126:4250-4261