A new pathologic pathway for pulmonary fibrosis induced by silica: involvement of immunosuppressive responses.

We have proposed that experimental lung fibrosis induced by silica particles is driven by immunosuppression in mice. We showed that the powerful anti-inflammatory cytokine interleukine-10 (IL-10) participates in the development of lung fibrosis by enhancing the expression of pro-fibrotic factors such TGF-beta, IL-4 and IL-13 and by reducing the production anti-fibrotic mediators such as prostaglandin E2. We also reported that Foxp3+ regulatory T cells, known to prevent the development of deleterious inflammatory reactions, are markedly accumulated in the lung and the thymus during the development of silica-induced lung fibrosis in mice. This population controls the intensity of particle-induced inflammatory response and also plays an important direct role in the fibrotic disease. Our findings suggest that in some experimental conditions and patients, immunosuppression instead of inflammation drives fibrotic disease. The mechanism governing immunosuppressive responses should lead to new therapeutic strategies and new diagnostic techniques of lung fibrosis.