CD11b+ and sca-1+ cells exert the main beneficial effects of systemically administered bone marrow-derivedmononuclear cells in a murinemodel of mixed Th2/Th17 allergic airway inflammation

Systemic administration of bone marrow-derived mononuclear cells (BMDMCs) or bone marrowderivedmesenchymal stromal cells (MSCs) reduces inflammation and airway hyperresponsiveness (AHR) in amurinemodel of Th2-mediated eosinophilic allergic airway inflammation. However, since BMDMCs are a heterogeneous population that includesMSCs, it is unclearwhether theMSCs alone are responsible for the BMDMC effects. To determine which BMDMC population(s) is responsible for ameliorating AHR and lung inflammation in a model of mixed Th2-eosinophilic and Th17-neutrophilic allergic airway inflammation, reminiscent of severe clinical asthma, BMDMCs obtained from normal C57Bl/6 mice were serially depleted of CD45, CD34, CD11b, CD3, CD19, CD31, or Sca-1 positive cells. The different resulting cell populations were then assessed for ability to reduce lung inflammation and AHR in mixed Th2/Th17 allergic airway inflammation induced by mucosal sensitization to and challenge with Aspergillus hyphal extract (AHE) in syngeneic C56Bl/6 mice. BMDMCs depleted of either CD11b-positive (CD11b+) or Sca-1-positive (Sca-1+) cells were unable to ameliorate AHR or lung inflammation in this model. Depletion of the other cell types did not diminish the ameliorating effects of BMDMC administration. In conclusion, in the current model of allergic inflammation, CD11b+ cells (monocytes, macrophages, dendritic cells) and Sca-1+ cells (MSCs) are responsible for the beneficial effects of BMDMCs.