title: Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice.
abstract: Bone marrow-derived mesenchymal stromal cells (BMSCs) mitigate inflammation in mouse models of acute lung injury. However, specific mechanisms of BMSC actions on CD4 T lymphocyte-mediated inflammation in vivo remain poorly understood. Limited data suggests promotion of Th2 phenotype in models of Th1-mediated diseases. However, whether this might alleviate or worsen Th2-mediated diseases such as allergic asthma is unknown. To ascertain the effects of systemic administration of BMSCs in a mouse model of Th2-mediated allergic airways inflammation, ovalbumin (OVA)-induced allergic airways inflammation was induced in wild-type C57BL/6 and BALB/c mice as well as in interferon-γ (IFNγ) receptor null mice. Effects of systemic administration during antigen sensitization of either syngeneic or allogeneic BMSC on airways hyperreactivity, lung inflammation, antigen-specific CD4 T lymphocytes, and serum immunoglobulins were assessed. Both syngeneic and allogeneic BMSCs inhibited airways hyperreactivity and lung inflammation through a mechanism partly dependent on IFNγ. However, contrary to existing data, BMSCs did not affect antigen-specific CD4 T lymphocyte proliferation but rather promoted Th1 phenotype in vivo as assessed by both OVA-specific CD4 T lymphocyte cytokine production and OVA-specific circulating immunoglobulins. BMSCs treated to prevent release of soluble mediators and a control cell population of primary dermal skin fibroblasts only partly mimicked the BMSC effects and in some cases worsened inflammation. In conclusion, BMSCs inhibit Th2-mediated allergic airways inflammation by influencing antigen-specific CD4 T lymphocyte differentiation. Promotion of a Th1 phenotype in antigen-specific CD4 T lymphocytes by BMSCs is sufficient to inhibit Th2-mediated allergic airways inflammation through an IFNγ-dependent process.
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
authors.forename: Meagan
authors.initials: M
authors.lastname: Goodwin
authors.forename: Viranuj
authors.initials: V
authors.lastname: Sueblinvong
authors.forename: Philip
authors.initials: P
authors.lastname: Eisenhauer
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Ziats
authors.forename: Laurie
authors.initials: L
authors.lastname: LeClair
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rincon
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D010047:Ovalbumin