Home
|
Inbox
|
Search
|
View Abstract
Resolution of Bleomycin-Induced Murine Pulmonary Fibrosis Via a Splenic Lymphocyte Subpopulation
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A5745 - Resolution of Bleomycin-Induced Murine Pulmonary Fibrosis Via a Splenic Lymphocyte Subpopulation
Author Block: K. Kamio, A. Azuma, K. Matsuda, J. Usuki, M. Inomata, A. Morinaga, T. Kashiwada, N. Nishijima, S. Itakura, N. Kokuho, K. Atsumi, H. Hayashi, T. Yamaguchi, K. Fujita, Y. Saito, S. Abe, K. Kubota, A. Gemma; Nippon Medical School, Tokyo, Japan.
Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality, and the pathogenesis of the disease is still incompletely understood. Although lymphocytes, especially CD4+CD25+FoxP3+ regulatory T cells (Tregs), have been implicated in the development of IPF, contradictory results have been reported regarding the contribution of Tregs to fibrosis both in animals and humans. The aim of this study was to investigate whether a specific T cell subset has therapeutic potential in inhibiting bleomycin (BLM)-induced murine pulmonary fibrosis. Methods: C57BL/6 mice received BLM (100 mg/kg body weight) with osmotic pumps (day 0), and pulmonary fibrosis was induced. Then, splenocytes or Tregs were adoptively transferred via the tail vein. The lungs were removed and subjected to histological and biochemical examinations to study the effects of these cells on pulmonary fibrosis, and blood samples were collected by cardiac punctures to measure relevant cytokines in enzyme-linked immunosorbent assay. To determine the roles of the spleen in this model, spleen vessels were carefully cauterized and the spleen was removed either on day 0 or 14 after a BLM challenge. Results: Splenocytes significantly ameliorated BLM-induced pulmonary fibrosis when they were administered on day 14. This effect was abrogated by depleting Tregs with an anti-CD25 monoclonal antibody. Adoptive transfer of Tregs on day 14 after a BLM challenge significantly attenuated pulmonary fibrosis, and this was accompanied by decreased production of fibroblast growth factor (FGF) 9 positive cells bearing the morphology of alveolar macrophages and epithelial cells. In addition, BLM-induced plasma interleukin (IL)-10 expression reverted to basal levels after adoptive transfer of Tregs. Moreover, BLM-induced fibrocyte chemoattractant chemokine (CC motif) ligand-2 (CCL2) was significantly ameliorated by Treg adoptive transfer in lung homogenates. Finally, splenectomy on day 14 after a BLM challenge significantly exacerbated lung fibrosis, whereas a splenectomy on day 0 ameliorated fibrosis. Conclusions: These findings warrant further investigations to develop a cell-based therapy using Tregs for treating IPF.
Author Block: K. Kamio, A. Azuma, K. Matsuda, J. Usuki, M. Inomata, A. Morinaga, T. Kashiwada, N. Nishijima, S. Itakura, N. Kokuho, K. Atsumi, H. Hayashi, T. Yamaguchi, K. Fujita, Y. Saito, S. Abe, K. Kubota, A. Gemma; Nippon Medical School, Tokyo, Japan.
Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality, and the pathogenesis of the disease is still incompletely understood. Although lymphocytes, especially CD4+CD25+FoxP3+ regulatory T cells (Tregs), have been implicated in the development of IPF, contradictory results have been reported regarding the contribution of Tregs to fibrosis both in animals and humans. The aim of this study was to investigate whether a specific T cell subset has therapeutic potential in inhibiting bleomycin (BLM)-induced murine pulmonary fibrosis. Methods: C57BL/6 mice received BLM (100 mg/kg body weight) with osmotic pumps (day 0), and pulmonary fibrosis was induced. Then, splenocytes or Tregs were adoptively transferred via the tail vein. The lungs were removed and subjected to histological and biochemical examinations to study the effects of these cells on pulmonary fibrosis, and blood samples were collected by cardiac punctures to measure relevant cytokines in enzyme-linked immunosorbent assay. To determine the roles of the spleen in this model, spleen vessels were carefully cauterized and the spleen was removed either on day 0 or 14 after a BLM challenge. Results: Splenocytes significantly ameliorated BLM-induced pulmonary fibrosis when they were administered on day 14. This effect was abrogated by depleting Tregs with an anti-CD25 monoclonal antibody. Adoptive transfer of Tregs on day 14 after a BLM challenge significantly attenuated pulmonary fibrosis, and this was accompanied by decreased production of fibroblast growth factor (FGF) 9 positive cells bearing the morphology of alveolar macrophages and epithelial cells. In addition, BLM-induced plasma interleukin (IL)-10 expression reverted to basal levels after adoptive transfer of Tregs. Moreover, BLM-induced fibrocyte chemoattractant chemokine (CC motif) ligand-2 (CCL2) was significantly ameliorated by Treg adoptive transfer in lung homogenates. Finally, splenectomy on day 14 after a BLM challenge significantly exacerbated lung fibrosis, whereas a splenectomy on day 0 ameliorated fibrosis. Conclusions: These findings warrant further investigations to develop a cell-based therapy using Tregs for treating IPF.
|
Home
|
Inbox
|
Search
|