While heredity is a primary predisposing factor for autoimmunity, cumulative exposures to environmental factors such as toxic stressors and diet greatly impact latency and severity autoimmune diseases such as lupus. Our goal is to understand how lupus triggering by an ubiquitous environmental toxicant can be prevented by dietary modulation of cellular lipids. This goal is predicated on preliminary studies revealing that 1)airway exposure to crystalline silica, a recognized autoimmune disease risk factor, triggers early onset of systemic autoimmunity and glomerulonephritis in the lupus-prone female NZBWF1 mouse and 2)supplementing their diets with the omega-3 fatty acid docosahexaenoic acid (DHA), a well-known dietary supplement extracted from cold-water fish, dose-dependently blocks this triggering. Here, we will employ in vitro, ex vivo, and in vivo approaches to test the hypothesis that DHA consumption prevents silica- triggered autoimmunity by suppressing inflammasome activation, cell death and self-antigen release in alveolar macrophages of NZBWF1 mice. Revealing DHA mechanisms against silica- triggered lupus will bring novel insights into how respiratory toxicants initiate lupus and subsequent flaring via lung as well as how manipulating cellular lipids through diet can be exploited to prevent environmental triggering of human autoimmune disease.

Public Health Relevance

Environmental exposure to earth?s most abundant mineral, crystalline silica (quartz), increases the risk of developing autoimmune diseases such as systemic lupus erythematosus (lupus). Here we seek to understand the underlying mechanisms by which consumption of the omega-3 fatty acid docosahexaenoic acid (DHA) blocks silica-triggered autoimmunity in the lupus-prone mouse model. This study will yield important new insights into how environmental toxicants trigger initiation/flaring of autoimmune diseases and how manipulating the lipidome through dietary fatty acid supplementation can prevent these events.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES027353-04
Application #
9944551
Study Section
Systemic Injury by Environmental Exposure (SIEE)
Program Officer
Humble, Michael C
Project Start
2017-06-01
Project End
2022-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Michigan State University
Department
Nutrition
Type
Earth Sciences/Resources
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824