Animal models used to examine the role of the environment in the development of autoimmune disease: Findings from an NIEHS Expert Panel Workshop

Abstract

Autoimmunity is thought to result from a combination of genetics, environmental triggers, and stochastic events. Environmental factors, such as chemicals, drugs or infectious agents, have been implicated in the expression of autoimmune disease, yet human studies are extremely limited in their ability to test isolated exposures to demonstrate causation or to assess pathogenic mechanisms. In this review we examine the research literature on the ability of chemical, physical and biological agents to induce and/or exacerbate autoimmunity in a variety of animal models. There is no single animal model capable of mimicking the features of human autoimmune disease, particularly as related to environmental exposures. An objective, therefore, was to assess the types of information that can be gleaned from the use of animal models, and how well that information can be used to translate back to human health. Our review notes the importance of genetic background to the types and severity of the autoimmune response following exposure to environmental factors, and emphasizes literature where animal model studies have led to increased confidence about environmental factors that affect expression of autoimmunity. A high level of confidence was reached if there were multiple studies from different laboratories confirming the same findings. Examples include mercury, pristane, and infection with Streptococcus or Coxsackie B virus. A second level of consensus identified those exposures likely to influence autoimmunity but requiring further confirmation. To fit into this category, there needed to be significant supporting data, perhaps by multiple studies from a single laboratory, or repetition of some but not all findings in multiple laboratories. Examples include silica, gold, TCE, TCDD, UV radiation, and Theiler’s murine encephalomyelitis virus. With the caveat that researchers must keep in mind the limitations and appropriate applications of the various approaches, animal models are shown to be extremely valuable tools for studying the induction or exacerbation of autoimmunity by environmental conditions and exposures.

Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

“…2,3 Silicosis is a brotic lung disease caused by the inhalation of silica dust. Occupational exposure to respirable silica particles occurs in many situations, which are oen called the dusty trades and include abrasive blasting with sand, jack hammering, drilling, mining/tunneling operations, and cutting and sawing.…”

Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus

“…To strengthen this hypothesis we have shown that IgG4 anti-Dsg1 autoAbs cross-react with LJM11 sand fly salivary gland antigen (13), which suggests that the development of IgG4 Abs may be linked to immune responses to environmental antigens. Compared to investigations on the pathogenesis and genetic predisposition of autoimmune diseases, etiological studies regarding environmental triggers of these diseases are lacking due to low prevalence and the clinical heterogeneity of the diseases (14–19). Similarly, the random nature of autoimmune skin diseases in North America makes it difficult to assess their etiological commonality and further dissect their causes.…”

Effects of Viral and Cytokine Delays on Dynamics of Autoimmunity

“…It is extremely difficult to identify the specific causes of autoimmunity in individual patients, as it usually has contributions from a number of internal and external factors, including a genetic predisposition, age, previous immune challenges, exposure to pathogens etc., [6][7][8][9]. Even though genetic predisposition is known to play a very significant role, it is believed that some additional environmental triggers are required for the onset of autoimmunity, and these are usually represented by infections [10,11]. A very recent work has experimentally identified a gut bacterium that, when present in mice and humans, can migrate to other parts of the body, facilitating subsequent triggering of autoimmune disease in those organs [12].…”