Open AccessBone Marrow‐Derived Mesenchymal Stromal Cells Inhibit Th2‐Mediated Allergic Airways Inflammation in Mice
Author(s) -
Goodwin Meagan,
Sueblinvong Viranuj,
Eisenhauer Philip,
Ziats Nicholas P.,
LeClair Laurie,
Poynter Matthew E.,
Steele Chad,
Rincon Mercedes,
Weiss Daniel J.
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.656
Subject(s) - immunology , inflammation , bone marrow , allergic inflammation , antigen , mesenchymal stem cell , ovalbumin , biology , stromal cell , cytokine , population , medicine , cancer research , microbiology and biotechnology , environmental health
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. S TEM C ELLS 2011;29:1137–1148