IL-3-producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model - Université d'Angers Accéder directement au contenu
Article Dans Une Revue Allergy Année : 2018

IL-3-producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model

Résumé

Background Basophils are commonly associated with allergic responses because of their ability to produce large amounts of pro‐Th2 cytokines and histamine. However, the mechanisms through which bone marrow‐resident basophils (BMRB) become fully competent cytokine and histamine producers in response to IgE crosslinking are poorly understood. Here, we sought to determine the role of IL‐3 in promoting pro‐Th2 basophils. Methods BMRB and basophils exposed to IL‐3 in vitro and in vivo were evaluated for their production of Th2 cytokines and histamine in response to FcεRI crosslinking on both protein and gene expression levels. In vivo relevance of our findings was assessed in a model of ovalbumin‐induced allergic asthma using IL‐3–deficient and wild‐type mice in a protocol of adoptive basophil transfer. Results We show that BMRB and basophils previously exposed to IL‐3 differ in their ability to generate cytokines (IL‐4, IL‐6, IL‐13, and GM‐CSF) and histamine in response to FcεRI crosslinking, reflecting two stages of maturation. Exposure to IL‐3 initiated an autocrine loop of endogenous IL‐3 production that enhanced histamine and cytokine production upon FcεRI crosslinking. This increased responsiveness required calcium flux and was dependent on calcineurin and store‐operated calcium channels. Our findings are of pathophysiological relevance, as assessed by the failure of IL‐3–deficient mice to develop airway hyperreactivity, which could be restored by adoptive transfer of IL‐3–derived basophils recovered from wild‐type mice. Conclusion IL‐3–dependent basophils promote Th2 allergic AHR, which designates the IL‐3/basophil axis as a promising therapeutic target for the treatment of basophil‐dependent asthma.
Fichier principal
Vignette du fichier
IL-3-Basophil-Bronchoconstriction.pdf (1.04 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-02571992 , version 1 (19-05-2020)

Identifiants

Citer

R. Rignault-Bricard, F. Machavoine, Salah Mecheri, O. Hermine, E. Schneider, et al.. IL-3-producing basophils are required to exacerbate airway hyperresponsiveness in a murine inflammatory model. Allergy, 2018, 73 (12), pp.2342-2351. ⟨10.1111/all.13480⟩. ⟨hal-02571992⟩
50 Consultations
288 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More