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Mesenchymal Stem Cells Recruit CCR2+ Monocytes To Suppress Allergic Airway Inflammation.

Authors
  • Takeda, Katsuyuki1
  • Webb, Tracy L2
  • Ning, Fangkun3
  • Shiraishi, Yoshiki3
  • Regan, Daniel P2
  • Chow, Lyndah2
  • Smith, Mia J2
  • Ashino, Shigeru3
  • Guth, Amanda M2
  • Hopkins, Sophie2
  • Gelfand, Erwin W3
  • Dow, Steven2
  • 1 Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206; and [email protected]
  • 2 Center for Immune and Regenerative Medicine, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523.
  • 3 Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206; and.
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Feb 15, 2018
Volume
200
Issue
4
Pages
1261–1269
Identifiers
DOI: 10.4049/jimmunol.1700562
PMID: 29352000
Source
Medline
License
Unknown

Abstract

Mesenchymal stem cells (MSC) exert immune modulatory properties and previous studies demonstrated suppressive effects of MSC treatment in animal models of allergic airway inflammation. However, the underlying mechanisms have not been fully elucidated. We studied the role of MSC in immune activation and subsequent recruitment of monocytes in suppressing airway hyperresponsiveness and airway inflammation using a mouse model of allergic airway inflammation. MSC administration prior to or after allergen challenge inhibited the development of airway inflammation in allergen-sensitized mice. This was accompanied by an influx of CCR2-positive monocytes, which were localized around injected MSC in the lungs. Notably, IL-10-producing monocytes and/or macrophages were also increased in the lungs. Systemic administration of liposomal clodronate or a CCR2 antagonist significantly prevented the suppressive effects of MSC. Activation of MSC by IFN-γ leading to the upregulation of CCL2 expression was essential for the suppressive effects, as administration of wild-type MSC into IFN-γ-deficient recipients, or IFN-γ receptor-deficient or CCL2-deficient MSC into wild-type mice failed to suppress airway inflammation. These results suggest that MSC activation by IFN-γ, followed by increased expression of CCL2 and recruitment of monocytes to the lungs, is essential for suppression by MSC in allergen-induced airway hyperresponsiveness and airway inflammation.

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