Pulmonary and systemic effects of inhaled crystalline silica in the HOCl-induced mouse model of systemic sclerosis: An experimental model of Erasmus syndrome.

Occupational exposure to crystalline silica is etiologically linked to an increased incidence of systemic sclerosis (SSc), also called Erasmus syndrome. The underlying mechanisms of silica-related SSc are still poorly understood. We demonstrated that early and repeated silica exposure contribute to the severity of SSc symptoms in the hypochloric acid (HOCl)-induced SSc mouse model. Analyses of lung samples from silica-exposed HOCl mice revealed a slightly aggravation of fibrosis and an exacerbation of inflammation, notably an additionally overexpression of NLRP3 inflammasome genes and a recruitment of classical monocytes, macrophages, dendritic cells and neutrophils. Silica exposure showed systemic effects in SSc mouse model with an elevated circulating classical monocyte counts and an overexpression of inflammatory genes in the skin. Silica-exposed SSc patients also had more severe skin disease than unexposed patients. Overall, we provide new insights on immune cell populations and related pathways in early pathogenic mechanisms contributing to HOCl-induced and silica-related SSc.