Colony-stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma.
Allergy
; 75(2): 357-369, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31385613
ABSTRACT
BACKGROUND:
A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation.OBJECTIVE:
To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallergens.METHODS:
We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe.RESULTS:
Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction.CONCLUSION:
The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Asma
/
Factor Estimulante de Colonias de Macrófagos
/
Sistemas de Liberación de Medicamentos
/
Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos
/
Anisoles
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Allergy
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos