SLAM-family receptors are a family of cell surface receptors that play a variety of roles during the generation of innate and adaptive immune responses. Type I interferons are key cytokines that promote antiviral immunity, but if dysregulated, can contribute to the development of autoimmune diseases such as systemic lupus erythematosus. One member of the SLAM-family, SLAMF9, appears to limit the production of type I interferons in response to Toll-like receptor stimulation. Our study aims to determine how SLAMF9 functions in the immune system and its role in regulating type I interferons during viral infection or other immune stimulation. Experiments will examine the regulation of type I interferon following in vivo administration of Toll-like receptor agonists or MCMV infection. Microscopic and flow cytometric analyses will establish the cellular distribution of this receptor, with special emphasis on those cells responsible for interferon production. Lastly, the cell intrinsic mechanisms for regulating type I interferon production by SLAMF9+ cells will be studied. Key to these studies will be the functional evaluation of plasmacytoid dendritic cells and yet undefined populations of CD11b+ SLAMF9+ cells in wild type and Slamf9-/- mice. These studies will contribute to our understanding of the roles of cell surface receptors in regulating antiviral immunity and will help define cellular and molecular targets for therapeutic manipulation of type I interferons.

Public Health Relevance

Type I interferons are soluble chemical messengers that promote antiviral immunity, but if dysregulated, can contribute to the development of autoimmune diseases such as systemic lupus erythematosus. We are examining the function of a cell surface protein that may limit the production of type I interferons during viral infection. Our study aims to determine how this functions in the immune system and its role in regulating type I interferons during viral infection or other immune challenge.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AI138184-01A1
Application #
9656484
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Minnicozzi, Michael
Project Start
2018-12-20
Project End
2021-11-30
Budget Start
2018-12-20
Budget End
2021-11-30
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Miami University Oxford
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
041065129
City
Oxford
State
OH
Country
United States
Zip Code
45056