Lupus flares when genetically predisposed people encounter certain environmental agents. How the environment alters the immune response to cause flares is unclear. The treatment of lupus is also imperfect, often requiring drugs with significant toxicities. Understanding how the environment causes lupus flares could indicate safer and more effective treatments. The lupus-inducing drugs procainamide and hydralazine, as well as oxidative stress such as that caused by UV light, silica and infections, inhibit T cell DNA methylation and increase expression of genes such as CDI l a , perforin, CD70, CD40L and KIR genes, converting normal

Public Health Relevance

Environmental agents associated with lupus alter the T cell epigenome, activating genes that convert normal T cells into autoreactive cells that cause lupus in mice. Similar changes characterize a T cell subset in patients with active lupus. This project characterizes the transcriptome and epigenome of this subset, with the goal of identifying targets for therapeutic approaches that eliminate or suppress the subset without affecting normal cells, improving the treatment of human lupus.

Agency
National Institute of Health (NIH)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI110502-01
Application #
8732927
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Figueroa-Romero, Claudia; Hur, Junguk; Lunn, J Simon et al. (2016) Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms. Mol Cell Neurosci 71:34-45
Namas, Rajaie; Renauer, Paul; Ognenovski, Mikhail et al. (2016) Histone H2AX phosphorylation as a measure of DNA double-strand breaks and a marker of environmental stress and disease activity in lupus. Lupus Sci Med 3:e000148
Tsou, Pei-Suen; Wren, Jonathan D; Amin, M Asif et al. (2016) Histone Deacetylase 5 Is Overexpressed in Scleroderma Endothelial Cells and Impairs Angiogenesis via Repression of Proangiogenic Factors. Arthritis Rheumatol 68:2975-2985
Delaney, Colin; Garg, Sanjay K; Yung, Raymond (2015) Analysis of DNA Methylation by Pyrosequencing. Methods Mol Biol 1343:249-64