title: Immunomodulation of airway epithelium cell activation by mesenchymal stromal cells ameliorates house dust mite-induced airway inflammation in mice.
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.
authors: 1 The School of Biomedical Sciences, The University of Queensland, Brisbane.
authors: Khang M
authors: KM
authors: Duong
authors: 1 The School of Biomedical Sciences, The University of Queensland, Brisbane.
authors: Jaisy
authors: J
authors: Arikkatt
authors: 2 The Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane.
authors: M Ashik
authors: MA
authors: Ullah
authors: 1 The School of Biomedical Sciences, The University of Queensland, Brisbane.
authors: Jason P
authors: JP
authors: Lynch
authors: 1 The School of Biomedical Sciences, The University of Queensland, Brisbane.
authors: Vivian
authors: V
authors: Zhang
authors: 3 The Queensland University of Technology at the Translational Research Institute, Brisbane.|4 The University of Queensland Centre for Clinical Research, Brisbane; and.
authors: Kerry
authors: K
authors: Atkinson
authors: 5 The Queensland Children's Medical Research Institute, The University of Queensland, Brisbane, Australia.
authors: Peter D
authors: PD
authors: Sly
authors: 1 The School of Biomedical Sciences, The University of Queensland, Brisbane.
authors: Simon
authors: S
authors: Phipps
mesh_terms: D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D004802:Eosinophilia / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D056747:Immunomodulation / Q000187:drug effects; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D053582:Interleukin-1alpha / Q000235:genetics / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D000485:Allergens; D018793:Interleukin-13; D053582:Interleukin-1alpha; D015848:Interleukin-5; D007378:Interleukins; C442281:Mydgf protein, mouse
keywords: HMGB1; IL-1α; IL-25; alarmin; asthma