Mesenchymal stromal cells mediate Aspergillus hyphal extract-induced allergic airway inflammation by inhibition of the Th17 signaling pathway.

[allergic bronchopulmonary aspergillosis]

Systemic administration of mesenchymal stromal cells (MSCs ) suppresses airway inflammation and methacholine-induced airway hyper-responsiveness (AHR ) in mouse models of T helper cell (Th ) type 2 -mediated eosinophilic allergic airway inflammation (AAI ); however , the efficacy of MSCs in mouse models of severe Th 17 -mediated neutrophilic AAI has not yet been demonstrated . We assessed MSC effects in a mouse model of mixed Th 2 /Th 17 AAI produced by mucosal exposure to Aspergillus fumigatus hyphal extract (AHE ). Following sensitization produced by oropharyngeal AHE administration , systemic (tail vein ) administration of syngeneic MSCs on the first day of challenge significantly reduced acute AHR predominantly through reduction of Th 17 -mediated airway inflammation . In parallel experiments , MSCs also mitigated AHR when administered during recurrent challenge 10 weeks after initial sensitization and challenge through reduction in systemic Th 17 -mediated inflammation . Investigation into potential mechanistic actions of MSCs in this model demonstrated that although T regulatory cells were increased in all AHE-treated mice , MSC administration did not alter T regulatory cell numbers in either the acute or recurrent model . Differential induction of interleukin-17 a secretion was observed in ex vivo restimulation of mediastinal lymph node mixed -cell cytokine analyses . Although the mechanisms by which MSCs act to decrease inflammation and AHR in this model are not yet fully elucidated , decrease in Th 17 -mediated airway inflammation appears to play a significant role . These results provide a basis for further investigations of MSC administration as a potential therapeutic approach for severe refractory neutrophilic asthma .

Diseases
Validation

Diseases presenting "first day" symptom

allergic bronchopulmonary aspergillosis

harlequin ichthyosis

homocystinuria without methylmalonic aciduria

lamellar ichthyosis

monosomy 21

pyruvate dehydrogenase deficiency

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