title: 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.affiliation: Department of Cardiovascular and Thoracic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Guo
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Qingshu
authors.initials: Q
authors.lastname: Meng
authors.forename: Hao
authors.initials: H
authors.lastname: Cao
authors.forename: Le
authors.initials: L
authors.lastname: Kang
authors.forename: Yinkai
authors.initials: Y
authors.lastname: Ni
authors.forename: Huimin
authors.initials: H
authors.lastname: Fan
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D002460:Cell Line; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000276:immunology; D014132:Trachea / Q000637:transplantation*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D016207:Cytokines