About this Research Topic
The immune system has evolved to directly destroy pathogens and host cells which have been infected with pathogens. More recently, it has become abundantly clear that the immune system can also target and destroy cancer cells. While the immune system is necessary to protect us, it must be strictly controlled so as to restrict collateral damage to non-infected normal cells and tissues. Accordingly, immune effector mechanisms including those involved in inflammatory responses, have co-evolved with an elaborate collection of multiple redundant checkpoints at different levels, collectively referred to as tolerance, which prevent or limit damage to healthy tissues and cells. Failure of these tolerogenic mechanisms leads to the development of autoimmune disease.
Autoimmune diseases can be organ-specific, systemic, or a combination of both. Individual autoimmune diseases are routinely clinically differentiated and classified according to the specificity and/or breadth of organ systems attacked. Much progress has been made over the last 50 years in elucidating the molecular and genetic underpinnings of specific checkpoint defects involved in many autoimmune diseases, often leading to the clinical use of small molecules and biologics to control autoimmune responses and to limit the deleterious outcomes for those who suffer from autoimmune diseases. Nevertheless, at this time it is impossible to say that we completely understand the etiology of any autoimmune disease, and in most instances, clinical interventions focus on alleviating symptoms, rather than providing cures.
One problem may be that naturally occurring autoimmune diseases likely represent a simultaneous failure of multiple checkpoints. Clinical interventions restoring function to one checkpoint may ignore others, or even inadvertently, decrease their functionality. In this sense, autoimmune diseases are seen to be multi-factorial. However, autoimmune diseases are also multi-factorial in a broader sense. Epidemiological studies have clearly shown that in addition to genetic factors, the development of autoimmune diseases depends critically upon environmental factors, including but not limited to, (i) the microbiome; (ii) viruses; (iii) diet; (iv) lifestyle, and (v) toxicants in the air, water and food. Presumably environmental factors influence multiple immune system checkpoints within the context of an individual’s unique genetics to trigger initiation and/or flaring, as well as to promot the progression of autoimmunity. Unfortunately, while knowledge of the genetics underlying many autoimmune diseases has rapidly advanced, research directed towards elucidating how exposure to environmental factors during our lifetime interact with these genetic aspects has lagged. Consequently, our understanding of autoimmune diseases is far from complete.
The aim of this Research Topics collection is to begin to remedy this imbalance by highlighting some of what we do know about environmental influences on autoimmune disease, and pointing the way to what needs to be done in the future. In this Research Topic, we welcome the submission of Original Research, Reviews, Mini-Reviews, Perspective, Opinion, Methods and Protocols that cover, but are not necessarily limited to the following topics:
1. Mechanisms by which environmental factors disrupt the immune system so as to initiate or exacerbate autoimmunity and autoimmune disease.
2. The functional consequence of the timing of exposure in disease formation, including characterization of critical windows in the timing of specific environmental exposures - such as during the fetal, perinatal, prepubertal, pubertal, adult and aged periods – in relation to the sensitivity to the development of autoimmune disease.
3. Functional consequences of environmentally-induced epigenetic changes in the development of autoimmunity.
4. The interplay between environmental exposures and the hormonal milieu in mediating sex differences in the incidence of autoimmune disease.
5. The role of the microbiome in autoimmunity.
6. The role of diet in autoimmunity.
7. Disease markers (biomarkers) of environmentally-induced autoimmunity.
8. Identification of susceptibility factors to environmentally-influenced autoimmune disease.
9. Epidemiological evidence connecting environmental influences with autoimmune disease.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.