Abstract

Funded RDCC Pilot and Feasibility Study #1 Title: Role of ISG15 in the pathogenesis of SLE PI: Deborah J. Lenschow, M.D., Ph.D. A.
Specific Aims : Systemic lupus erythematosis (SLE) is a chronic autoimmune disease characterized by the loss of tolerance to nuclear antigens and the development of pathogenic autoantibodies, resulting in injury to multiple organ systems. Recent studies have implicated type I interferons (IFNs) in the pathogenesis of SLE;however, the downstream IFN effector molecules that mediate these actions are poorly understood. We proposed the following aims to evaluate the role of a recently identified and characterized IFN induced molecule, ISG15, in the pathogenesis of SLE.
Aim 1. Determine if ISG15 functions as a cytokine to regulate immune responses.
Aim 2. Determine if ISG15 plays a role in the pathogenesis of SLE. During the course of these studies it became apparent that while IFNs are known to play a role in the pathogenesis of SLE in various murine models, little is known about the cell type specific effects of this class of cytokines in these models. We have obtained or are developing reagents for other projects in the lab that will allow us to evaluate cell type specific effects of type I IFNs. We propose to utilize these reagents to pursue this question in murine models of SLE.
Aim 3. Determine the cell type specific effects of Type I IFNs in the pathogenesis of SLE.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR048335-09
Application #
7918815
Study Section
Special Emphasis Panel (ZAR1)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
9
Fiscal Year
2009
Total Cost
$89,657
Indirect Cost

  Institution

Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Paing, May M; Salinas, Nichole D; Adams, Yvonne et al. (2018) Shed EBA-175 mediates red blood cell clustering that enhances malaria parasite growth and enables immune evasion. Elife 7:
Wilke, Georgia; Ravindran, Soumya; Funkhouser-Jones, Lisa et al. (2018) Monoclonal Antibodies to Intracellular Stages of Cryptosporidium parvum Define Life Cycle Progression In Vitro. mSphere 3:
Kulkarni, Hrishikesh S; Elvington, Michelle L; Perng, Yi-Chieh et al. (2018) Intracellular C3 Protects Human Airway Epithelial Cells from Stress-Associated Cell Death. Am J Respir Cell Mol Biol :
Garber, Charise; Vasek, Michael J; Vollmer, Lauren L et al. (2018) Astrocytes decrease adult neurogenesis during virus-induced memory dysfunction via IL-1. Nat Immunol 19:151-161
Yokoyama, Christine C; Baldridge, Megan T; Leung, Daisy W et al. (2018) LysMD3 is a type II membrane protein without an in vivo role in the response to a range of pathogens. J Biol Chem 293:6022-6038
Wu, Xiaobo; Hutson, Irina; Akk, Antonina M et al. (2018) Contribution of Adipose-Derived Factor D/Adipsin to Complement Alternative Pathway Activation: Lessons from Lipodystrophy. J Immunol 200:2786-2797
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Roberson, Elisha D O (2018) Motif scraper: a cross-platform, open-source tool for identifying degenerate nucleotide motif matches in FASTA files. Bioinformatics 34:3926-3928
Liszewski, M Kathryn; Elvington, Michelle; Kulkarni, Hrishikesh S et al. (2017) Complement's hidden arsenal: New insights and novel functions inside the cell. Mol Immunol 84:2-9

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