Long term overexpression of IL-10 increases recruitment of fibrocyte into the lung and induces fibrosis (48.5)

Abstract

Abstract Pulmonary fibrosis is characterized by the progressive deposition of extracellular matrix components such as collagen and fibronectin by fibroblasts and myofibroblasts. Three potential sources of fibroblasts and myofibroblasts include: expansion of resident lung fibroblasts, epithelial-mesenchymal transition, or recruitment and differentiation of circulating mesenchymal precursors (fibrocytes). IL-10 is a well-known immunosuppressive cytokine and in some studies has an inhibitory effect on fibrosis, however, this is less well studied. In our study, long-term overexpression of IL-10 (IL-10 OE) induced fibrosis. The total cell number from bronchoalveolar lavage (BAL) increased ten-fold in the IL-10 OE mice, with significant infiltration of T, B lymphocytes and collagen-producing cells. Fibrocytes from collagenase digested lung were identified by flow cytometry with dual staining of CD45 and collagen 1. IL-10 OE increased whole lung fibrocyte numbers by two-fold. Q-PCR analysis on an array of chemokine/chemokine receptor genes showed that only CCL2 and CCL2 receptor (CCR2) were highly upregulated in IL-10 OE mice, suggesting that IL-10 induced fibrocyte recruitment is CCL2/CCR2 specific. We also examined M2 macrophage activation and found significant numbers of M2 macrophages in both BAL and whole lung tissue from the IL-10 OE mice. Taken together, long term overexpression of IL-10 may induce fibrosis, in part, by fibrocyte recruitment and M2 macrophage activation.