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

Abstract : 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.
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https://hal.univ-angers.fr/hal-02571992
Contributeur : Salah Mecheri <>
Soumis le : mardi 19 mai 2020 - 15:01:29
Dernière modification le : dimanche 13 septembre 2020 - 22:50:02

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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, Wiley, 2018, 73 (12), pp.2342-2351. ⟨10.1111/all.13480⟩. ⟨hal-02571992⟩

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