The Impact of Paternal Exposure to Environment on Susceptibility to Lupus
Abstract
Lupus is an autoimmune disorder in which the immune system inadvertently recognizes the body’s tissues as foreign, resulting in the production of autoantibodies that can result into a range clinical symptoms from rash, to arthritis to kidney failure. Lupus is known to be a genetic disease. However, genetics is only one factor, and there are strong indications that environmental cues also play a substantial role. Environmental factors such as exposure to microorganisms, toxins, or organic pollutants as well as diet have all been linked to this disease. These factors are thought to push individuals over the line from just being genetically at risk, toward development of full-blown lupus. Complicating this is the possibility of transgenerational impacts of environment. That is, interaction of a parent with environmental factors, which then manifests in their offspring. Indeed, there have been increasing reports of environmental factors affecting the development of a range of autoimmune diseases via mothers. Even more surprisingly, there is now evidence suggesting that interactions of fathers with environmental factors can also manifest in offspring via changes in the sperm, although a connection with autoimmunity has not been explored. Thus, predicting the likelihood of developing disease is not as simple as genetic mapping, and dissecting the role of environmental factors is critical. The goal of this project is to determine if environment can indeed indirectly influence the development of lupus via fathers. This hypothesis will be tested in established mouse models of the disease. This proposal addresses Fiscal Year 2018 Lupus Research Program Focus Area #1 of understanding disease heterogeneity, because the heterogeneity of the disease may in large part be due to the different environmental factors to which individuals are exposed. If we can demonstrate that environment does indeed have transgenerational effects on lupus, this would be a paradigm-shift in our understanding of the pathogenesis of the disease. This immediately opens up the possibility of translating to humans, where we can start to map potential associations between patients and their parents. Ultimately, if can make a link with specific environmental factors, we can potentially reduce disease incidence by reducing exposure to these factors. Furthermore, if we can determine how such environmental factors actually potentiate disease at the molecular level, then this understanding will point to targets for therapeutic intervention(s).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910728
Entities
People
- Mark M. Chong
Organizations
- St. Vincent's Institute of Medical Research
- United States Army