PMID- 21544902 OWN - NLM STAT- MEDLINE DCOM- 20111115 LR - 20211020 IS - 1549-4918 (Electronic) IS - 1066-5099 (Print) IS - 1066-5099 (Linking) VI - 29 IP - 7 DP - 2011 Jul TI - Bone marrow-derived mesenchymal stromal cells inhibit Th2-mediated allergic airways inflammation in mice. PG - 1137-48 LID - 10.1002/stem.656 [doi] AB - 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-gamma (IFNgamma) 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 IFNgamma. 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 IFNgamma-dependent process. CI - Copyright (c) 2011 AlphaMed Press. FAU - Goodwin, Meagan AU - Goodwin M AD - Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. FAU - Sueblinvong, Viranuj AU - Sueblinvong V FAU - Eisenhauer, Philip AU - Eisenhauer P FAU - Ziats, Nicholas P AU - Ziats NP FAU - LeClair, Laurie AU - LeClair L FAU - Poynter, Matthew E AU - Poynter ME FAU - Steele, Chad AU - Steele C FAU - Rincon, Mercedes AU - Rincon M FAU - Weiss, Daniel J AU - Weiss DJ LA - eng GR - T32 HL076122/HL/NHLBI NIH HHS/United States GR - P20 RR-155557/RR/NCRR NIH HHS/United States GR - HL081289/HL/NHLBI NIH HHS/United States GR - R21 HL081289/HL/NHLBI NIH HHS/United States GR - R21 HL087274/HL/NHLBI NIH HHS/United States GR - HL087274/HL/NHLBI NIH HHS/United States GR - T32 HL76122/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Stem Cells JT - Stem cells (Dayton, Ohio) JID - 9304532 RN - 0 (Epitopes, T-Lymphocyte) RN - 82115-62-6 (Interferon-gamma) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Cell Differentiation/immunology MH - Disease Models, Animal MH - Epitopes, T-Lymphocyte/immunology MH - Female MH - Inflammation/immunology MH - Interferon-gamma/immunology MH - Male MH - Mesenchymal Stem Cells/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Ovalbumin/immunology MH - Respiratory Hypersensitivity/*immunology MH - Th2 Cells/*immunology PMC - PMC4201366 MID - NIHMS392305 EDAT- 2011/05/06 06:00 MHDA- 2011/11/16 06:00 PMCR- 2014/10/17 CRDT- 2011/05/06 06:00 PHST- 2011/05/06 06:00 [entrez] PHST- 2011/05/06 06:00 [pubmed] PHST- 2011/11/16 06:00 [medline] PHST- 2014/10/17 00:00 [pmc-release] AID - 10.1002/stem.656 [doi] PST - ppublish SO - Stem Cells. 2011 Jul;29(7):1137-48. doi: 10.1002/stem.656.