Exposure to air pollution does influence autoimmunity by triggering several autoimmune responses and amplifying systematic inflammation. A primary hypothesis that addresses the link claims that exposure to polluted air may excite T cell imbalance, accelerate the production of pro-inflammatory cytokines, exhibit local pulmonary inflammation, oxidative stress and methylation changes may explain the effect of air pollution on the pathogenesis autoimmune diseases.
Autoimmune diseases have been associated to be a subclass of the autoimmune/inflammatory syndrome which is generally triggered by adjuvants (ASIA). Furthermore, these are defined as a combination of the autoimmune conditions/phenomena which are stimulated when exposed to substances possessing adjuvant characteristics. Adjuvants may serve as triggers of various pathological entities of autoimmune etiology.
For instance, aluminium can trigger the formation of inflammatory signals which in turn causes a mismatch in the metal balance within the cytoplasm ultimately leading to mitochondrial failure and generation of reactive oxygen species.
On an additional note, the neurotoxicity of aluminium may induce brain inflammation gliosis and is thus primarily responsible for multiple sclerosis. Similarly smoke can inherently develop oxidative stress, disruption of the lung microenvironment and even facilitate infections and epigenetic changes to trigger the development of an autoimmune condition.
Air pollutants, as described in several recent pieces of research, can also act as adjuvants accelerating the development of the autoimmune syndrome. High exposure to air pollution can develop cascade reactions within the antigen-presenting cells and T lymphocytes. The presence of reactive metals and associated volatile materials generates free-radical which automatically initiates the NF-kB and MAP kinase pathways.
Higher exposure to particulate matter (above 2.5) aids in the development of the mRNA of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor. Moreover, the sulfur dioxide and the monoxides help in the formation of the Serum-IL-6 which is responsible for the increase in the cytokines. The local pulmonary inflammation may occur in the pathogenesis of the autoimmune disease by two probable mechanistic pathways.
Air pollution was reported with a sharp rise in oxidative stress in the airways, inducing the nuclear factor kappaB (NF-kB), and stimulating the production of T helper lymphocytes type 1 (Th1). The oxidative stress not only does stimulate the alveolar macrophages and airway epithelial cells to express pro-inflammatory cytokines but also causes the dendritic cells to travel to the lymph nodes resulting in cell necrosis and apoptosis accompanied with increased IL-17 and interleukin-23 (IL-23) levels.
The Aryl Hydrocarbon receptor pathway has a link in the inflammatory process and tunes the balance between effectors and regulatory T cells, thus ultimately participates in the process of the pathogenesis. The receptor-ligand is an activated complex transcription factor that behaves in accordance with the toxicants present along with the particulate matter.
The particulate matters have an increased level of the Aryl Hydrocarbon receptor ligands possible generating the Treg induction, augment Th17 differentiation and regulate autoimmunity. In vivo study showed that particulate matter accelerated the Th17 differentiation by acting on the Aryl Hydrocarbon receptor in T cells.
Any short time exposure to particulate matter with an index of 2.5 or higher may cause the methylation of at the CpG loci of the corresponding inflation genes to go down and thus consequently influences the inflammation behavior and contributes to autoimmune diseases.