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Immunostimulation by environmental and occupational factors has been shown to cause various human diseases such as allergy and autoimmune diseases [1,2]. For example, solvents such as vinyl chloride have been linked to the development of scleroderma (SSc) [3-5], and previous studies reported the relationship between exposure to solvents and rheumatoid arthritis (RA) [6] or multiple sclerosis [7,8]. Another typical substance is silica. Patients exposed to silica particles were shown to develop not only pulmonary fibrosis, known as silicosis [9,10], one of the typical forms of pneumoconiosis, but also various autoimmune diseases [11,12] such as RA (historically known as Caplan syndrome) [13,14], SSc [15-17], systemic lupus erythem‐ atous (SLE) [18,19], and anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis/ nephritis [20-22]. Many epidemiological reports have demonstrated that silica exposure is a risk factor of autoimmune diseases [11,12].

Immunostimulation by Silica Particles and the Development of Autoimmune Dysregulation