Immune Netw.  2015 Jun;15(3):142-149. 10.4110/in.2015.15.3.142.

Osteopontin Potentiates Pulmonary Inflammation and Fibrosis by Modulating IL-17/IFN-gamma-secreting T-cell Ratios in Bleomycin-treated Mice

Affiliations
  • 1Laboratory of Immunology and Cancer Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Korea. dlee5522@snu.ac.kr
  • 2Transplantation Research Institute, Seoul National University College of Medicine, Seoul 110-799, Korea.
  • 3Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea.

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.

Keyword

Osteopontin; Pulmonary fibrosis; alphabeta T cells; IL-17; Th17 differentiation

MeSH Terms

Animals
Bleomycin
Bone Marrow Cells
Fibrosis*
Inflammation
Interleukin-17
Lung
Mice*
Osteopontin*
Pneumonia*
Pulmonary Fibrosis
T-Lymphocytes*
T-Lymphocytes, Helper-Inducer
Bleomycin
Interleukin-17
Osteopontin
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