Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells

Louisa Mathias, Sacha M L Khong, Lisa Garifalia Spyroglou, Natalie Lisa Payne, Christopher Siatskas, Alison Nicole Thorburn, Richard Lennox Boyd, Tracy Shu Ping Heng

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

Multipotent mesenchymal stromal cells (MSCs) possess reparative and immunoregulatory properties, making them attractive candidates for cellular therapy. However, the majority of MSCs administered i.v. encounter a pulmonary impasse and soon disappear from the lungs, raising the question of how they induce such durable immunosuppressive effects. Using a mouse model of allergic asthma, we show that administration of MSCs isolated from human bone marrow, umbilical cord, or adipose tissue provoked a pronounced increase in alveolar macrophages and inhibited hallmark features of asthma, including airway hyperresponsiveness, eosinophilic accumulation, and Th2 cytokine production. Importantly, selective depletion of this macrophage compartment reversed the therapeutic benefit of MSC treatment on airway hyperresponsiveness. Our data demonstrate that human MSCs exert cross-species immunosuppressive activity, which is mediated by alveolar macrophages in allergic asthma. As alveolar macrophages are the predominant immune effector cells at the air-tissue interface in the lungs, this study provides a compelling mechanism for durable MSC effects in the absence of sustained engraftment.
Original languageEnglish
Pages (from-to)5914 - 5924
Number of pages11
JournalJournal of Immunology
Volume191
Issue number12
DOIs
Publication statusPublished - 2013

Cite this

Mathias, Louisa ; Khong, Sacha M L ; Spyroglou, Lisa Garifalia ; Payne, Natalie Lisa ; Siatskas, Christopher ; Thorburn, Alison Nicole ; Boyd, Richard Lennox ; Heng, Tracy Shu Ping. / Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells. In: Journal of Immunology. 2013 ; Vol. 191, No. 12. pp. 5914 - 5924.
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abstract = "Multipotent mesenchymal stromal cells (MSCs) possess reparative and immunoregulatory properties, making them attractive candidates for cellular therapy. However, the majority of MSCs administered i.v. encounter a pulmonary impasse and soon disappear from the lungs, raising the question of how they induce such durable immunosuppressive effects. Using a mouse model of allergic asthma, we show that administration of MSCs isolated from human bone marrow, umbilical cord, or adipose tissue provoked a pronounced increase in alveolar macrophages and inhibited hallmark features of asthma, including airway hyperresponsiveness, eosinophilic accumulation, and Th2 cytokine production. Importantly, selective depletion of this macrophage compartment reversed the therapeutic benefit of MSC treatment on airway hyperresponsiveness. Our data demonstrate that human MSCs exert cross-species immunosuppressive activity, which is mediated by alveolar macrophages in allergic asthma. As alveolar macrophages are the predominant immune effector cells at the air-tissue interface in the lungs, this study provides a compelling mechanism for durable MSC effects in the absence of sustained engraftment.",
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Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells. / Mathias, Louisa; Khong, Sacha M L; Spyroglou, Lisa Garifalia; Payne, Natalie Lisa; Siatskas, Christopher; Thorburn, Alison Nicole; Boyd, Richard Lennox; Heng, Tracy Shu Ping.

In: Journal of Immunology, Vol. 191, No. 12, 2013, p. 5914 - 5924.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Mathias, Louisa

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AU - Spyroglou, Lisa Garifalia

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AU - Thorburn, Alison Nicole

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AU - Heng, Tracy Shu Ping

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AB - Multipotent mesenchymal stromal cells (MSCs) possess reparative and immunoregulatory properties, making them attractive candidates for cellular therapy. However, the majority of MSCs administered i.v. encounter a pulmonary impasse and soon disappear from the lungs, raising the question of how they induce such durable immunosuppressive effects. Using a mouse model of allergic asthma, we show that administration of MSCs isolated from human bone marrow, umbilical cord, or adipose tissue provoked a pronounced increase in alveolar macrophages and inhibited hallmark features of asthma, including airway hyperresponsiveness, eosinophilic accumulation, and Th2 cytokine production. Importantly, selective depletion of this macrophage compartment reversed the therapeutic benefit of MSC treatment on airway hyperresponsiveness. Our data demonstrate that human MSCs exert cross-species immunosuppressive activity, which is mediated by alveolar macrophages in allergic asthma. As alveolar macrophages are the predominant immune effector cells at the air-tissue interface in the lungs, this study provides a compelling mechanism for durable MSC effects in the absence of sustained engraftment.

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