Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice

Duong, Khang M., Arikkatt, Jaisy, Ullah, M. Ashik, Lynch, Jason P., Zhang, Vivian, Atkinson, Kerry, Sly, Peter D. and Phipps, Simon (2015) Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice. American Journal of Respiratory Cell and Molecular Biology, 53 5: 615-624. doi:10.1165/rcmb.2014-0431OC


Author Duong, Khang M.
Arikkatt, Jaisy
Ullah, M. Ashik
Lynch, Jason P.
Zhang, Vivian
Atkinson, Kerry
Sly, Peter D.
Phipps, Simon
Title Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice
Journal name American Journal of Respiratory Cell and Molecular Biology   Check publisher's open access policy
ISSN 1044-1549
1535-4989
Publication date 2015-11
Sub-type Article (original research)
DOI 10.1165/rcmb.2014-0431OC
Open Access Status Not Open Access
Volume 53
Issue 5
Start page 615
End page 624
Total pages 10
Place of publication New York, United States
Publisher American Thoracic Society
Collection year 2016
Language eng
Formatted abstract
Allergic asthma is underpinned by T helper 2 (Th2) inflammation. Redundancy in Th2 cytokine function and production by innate and adaptive immune cells suggests that strategies aimed at immunomodulation may prove more beneficial. Hence, we sought to determine whether administration of mesenchymal stromal cells (MSCs) to house dust mite (HDM) (Dermatophagoides pteronyssinus)-sensitized mice would suppress the development of Th2 inflammation and airway hyperresponsiveness (AHR) after HDM challenge. We report that the intravenous administration of allogeneic donor MSCs 1 hour before allergen challenge significantly attenuated the features of allergic asthma, including tissue eosinophilia, Th2 cytokine (IL-5 and IL-13) levels in bronchoalveolar lavage fluid, and AHR. The number of infiltrating type 2 innate lymphoid cells was not affected by MSC transfer, suggesting that MSCs may modulate the adaptive arm of Th2 immunity. The effect of MSC administration was long lasting; all features of allergic airway disease were significantly suppressed in response to a second round of HDM challenge 4 weeks after MSC administration. Further, we observed that MSCs decreased the release of epithelial cell–derived alarmins IL-1α and high mobility group box-1 in an IL-1 receptor antagonist–dependent manner. This significantly decreased the expression of the pro-Th2 cytokine IL-25 and reduced the number of activated and antigen-acquiring CD11c+CD11b+ dendritic cells in the lung and mediastinal lymph nodes. Our findings suggest that MSC administration can ameliorate allergic airway inflammation by blunting the amplification of epithelial-derived inflammatory cytokines induced by HDM exposure and may offer long-term protection against Th2-mediated allergic airway inflammation and AHR.
Keyword Asthma
IL-1 alpha
Hmgb1
Il-25
Alarmin
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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