Mesenchymal stem cells reprogram host macrophages to attenuate obliterative bronchiolitis in murine orthotopic tracheal transplantation.

Abstract

After lung transplantation, obliterative bronchiolitis (OB) is one of the major limitations for the long-term survival of allografts. At present, effective treatment to prevent this phenomenon remains elusive. Mesenchymal stem cells (MSCs) are capable of modulating the immune system through the interaction with a wide range of immune cells. Here, we found that treatment of mice with bone marrow derived MSCs prevents the development of airway occlusion and increased IL-10 levels in trachea grafts, which was eliminated by the depletion of macrophages. Mechanistically, MSCs-derived PGE2, through the receptors EP2 and EP4, promoted the release of IL-10 and inhibited the production of IL-6 and TNF-α by macrophages. These results suggest that MSCs can both decrease the innate inflammatory responses and prevent allograft rejection by down-regulating the levels of IL-6 and TNF-α and increasing IL-10 production respectively. For easy availability and immune privilege, MSC-based treatment of OB provides an effective strategy for regulation of immune responses in lung transplantation.

• Authors: Zhixiang Guo, Xiaohui Zhou, Jing Li, Qingshu Meng, Hao Cao, Le Kang, Yinkai Ni, Huimin Fan, Zhongmin Liu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 15 Issue 4 Pg. 726-34 (Apr 2013) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 23499643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines

Topics

• Animals
• Bronchiolitis Obliterans (etiology, immunology, prevention & control)
• Cell Line
• Coculture Techniques
• Cytokines (biosynthesis, immunology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Macrophages, Alveolar (immunology)
• Male
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Phagocytosis (immunology)
• Trachea (transplantation)
• Transplantation Immunology
• Transplantation, Homologous
• Transplantation, Isogeneic