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

Allergy
R Rignault-BricardMaria C Leite-de-Moraes

Abstract

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. 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. 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 a...Continue Reading

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Citations

Feb 17, 2019·International Journal of Molecular Sciences·Francesco BorrielloGianni Marone
Jun 11, 2020·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Zhenxing XuWei Guo
Oct 6, 2020·Frontiers in Immunology·Giancarlo MaroneGilda Varricchi
Nov 19, 2020·Allergy·Kensuke MiyakeHajime Karasuyama
Dec 15, 2020·Current Allergy and Asthma Reports·Gabija DrazdauskaitėMohamed H Shamji
May 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Luciana P TavaresFrancesca Levi-Schaffer
Mar 18, 2021·Proceedings of the National Academy of Sciences of the United States of America·Christophe PellefiguesGraham Le Gros

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