Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

Krisztian Nemeth, Andrea Keane-Myers, Jared M. Brown, Dean D. Metcalfe, Jared D. Gorham, Victor G. Bundoc, Marcus G. Hodges, Ivett Jelinek, Satish Madala, S. Kárpáti, Eva Mezey

Research output: Contribution to journalArticle

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Abstract

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/ or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-β production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions - specifically therapy resistant asthma - might also be a likely target of the recently discovered cellular therapy approach using BMSCs.

Original languageEnglish
Pages (from-to)5652-5657
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number12
DOIs
Publication statusPublished - Mar 23 2010

Fingerprint

Ambrosia
Mesenchymal Stromal Cells
Interleukin-13
Asthma
Bronchoalveolar Lavage
Graft vs Host Disease
Interleukin-4
Cytokines
Immunomodulation
Interleukin-5
Regulatory T-Lymphocytes
Mucus
Serum
Eosinophils
Knockout Mice
Immunoglobulin E
Autoimmune Diseases
Immunoglobulins
Immunoglobulin G
Antigens

Keywords

  • Allergy
  • Cellular therapy
  • Immunomodulation
  • Mesenchymal stem cell

ASJC Scopus subject areas

  • General

Cite this

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma. / Nemeth, Krisztian; Keane-Myers, Andrea; Brown, Jared M.; Metcalfe, Dean D.; Gorham, Jared D.; Bundoc, Victor G.; Hodges, Marcus G.; Jelinek, Ivett; Madala, Satish; Kárpáti, S.; Mezey, Eva.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 12, 23.03.2010, p. 5652-5657.

Research output: Contribution to journalArticle

Nemeth, K, Keane-Myers, A, Brown, JM, Metcalfe, DD, Gorham, JD, Bundoc, VG, Hodges, MG, Jelinek, I, Madala, S, Kárpáti, S & Mezey, E 2010, 'Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 12, pp. 5652-5657. https://doi.org/10.1073/pnas.0910720107
Nemeth, Krisztian ; Keane-Myers, Andrea ; Brown, Jared M. ; Metcalfe, Dean D. ; Gorham, Jared D. ; Bundoc, Victor G. ; Hodges, Marcus G. ; Jelinek, Ivett ; Madala, Satish ; Kárpáti, S. ; Mezey, Eva. / Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 12. pp. 5652-5657.
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