Perspective: The Lung, Particles, Fibers, Nanomaterials, and Autoimmunity

Abstract

Studies have shown that a wide range of factors including drugs, chemicals, microbes, and other environmental agents can induce pre-clinical autoimmunity. However, only a few have been confidently linked to autoimmune diseases. Among these are exposures to inhaled particulates that are known to be associated with autoimmune diseases such as lupus and rheumatoid arthritis. In this article, the potential of particle, fiber, and nanomaterial exposures to induce autoimmunity is discussed. It is hypothesized that inhalation of particulate material known to be associated with human autoimmune diseases, such as cigarette smoke and crystalline silica, results in a complex interplay of a number of pathological processes, including, toxicity, oxidative stress, cell and tissue damage, chronic inflammation, post-translational modification of self-antigens, and the formation of lymphoid follicles that provide a milieu for the accumulation of autoreactive B and T cells necessary for the development and persistence of autoimmune responses, leading to disease. Although experimental studies show nanomaterials are capable of inducing several of the above features, there is no evidence that this matures to autoimmune disease. The procession of events hypothesized here provides a foundation from which to pursue experimental studies to determine the potential of other environmental exposures to induce autoimmunity and autoimmune disease.

The role of environmental exposures and gene–environment interactions in the etiology of systemic lupus erythematous

“…Recent experimental research upholds the observed association of silica with human SLE, as recently reviewed by Pollard, providing insight into the underlying mechanisms [40]. Inhaled respirable particulates escaping clearance enter a cycle of inflammation, apoptosis, and release of intracellular antigens, with increases in pro‐inflammatory cytokines, oxidative stress, and T‐cell responses and decreases in the number of regulatory T cells [41].…”

Blood Cadmium Levels and Oxygen Desaturation during the 6-Minute Walk Test in Patients with Chronic Obstructive Pulmonary Disease

“…Cadmium exposure could induce oxidative stress, cell and tissue damage, and generate reactive oxygen species, activate apoptosis, induce endoplasmic reticulum stress and persistent chronic inflammation, disrupt extracellular matrix homeostasis, and contribute to post-translational modification of self-antigens (e.g., protein citrullination), and the formation of lymphoid follicles that contribute to the accumulation of autoreactive B and T cells, necessary for the development and persistence of autoimmune responses [19,25,26]. All of these alternations are potentially responsible for the pathogenesis of COPD, impaired lung function, and reduced gas exchange [4,5,27].…”

New Insights into Pathomechanisms and Treatment Possibilities for Lung Silicosis

“…Although the molecular mechanisms of silica-induced inflammation, fibrosis, and the related autoimmune responses have not been completely understood yet, there has been a generally accepted concept supporting the contribution of inflammation in the development of fibrosis and autoimmune responses due to silica inhalation [2,9,73,74].…”

“…High production of profibrotic substances and recruitment of collagen-and fibronectinproducing cells, then, leads to the formation of silicotic nodules, scaring of the tissue, and reduction of areas for gas exchange. Due to the defect in an apoptotic cell clearance (or efferocytosis), a key process in the resolution of inflammation, silica-induced cellular death is a source of autoantigenic material, leading to the generation of autoantibodies and an autoimmune response [1,73,82].…”