Osteopontin Potentiates Pulmonary Inflammation and Fibrosis by Modulating IL-17/IFN-gamma-secreting T-cell Ratios in Bleomycin-treated Mice.
- Author:
Keunhee OH
1
;
Myung Won SEO
;
Young Whan KIM
;
Dong Sup LEE
Author Information
- Publication Type:In Vitro ; Original Article
- Keywords: Osteopontin; Pulmonary fibrosis; alphabeta T cells; IL-17; Th17 differentiation
- MeSH: Animals; Bleomycin; Bone Marrow Cells; Fibrosis*; Inflammation; Interleukin-17; Lung; Mice*; Osteopontin*; Pneumonia*; Pulmonary Fibrosis; T-Lymphocytes*; T-Lymphocytes, Helper-Inducer
- From:Immune Network 2015;15(3):142-149
- CountryRepublic of Korea
- Language:English
- Abstract: Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPN-deficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of CD4+ alphabeta T cells and IL-17-producing gammadelta T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of CD4+ alphabeta T cells and the percentage of IFN-gamma-producing gammadelta T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in CD4+ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-gamma T cells.
