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DOI10.1073/pnas.2019524118
Diverse innate stimuli activate basophils through pathways involving Syk and IκB kinases
Pellefigues C.; Mehta P.; Chappell S.; Yumnam B.; Old S.; Camberis M.; Le Gros G.
发表日期2021
ISSN00278424
卷号118期号:12
英文摘要Mature basophils play critical inflammatory roles during helminthic, autoimmune, and allergic diseases through their secretion of histamine and the type 2 cytokines interleukin 4 (IL-4) and IL-13. Basophils are activated typically by allergen-mediated IgE cross-linking but also by endogenous “innate” factors. The aim of this study was to identify the innate stimuli (cytokines, chemokines, growth factors, hormones, neuropeptides, metabolites, and bacterial products) and signaling pathways inducing primary basophil activation. Basophils from naïve mice or helminth-infected mice were cultured with up to 96 distinct stimuli and their influence on basophil survival, activation, degranulation, and IL-4 or IL-13 expression were investigated. Activated basophils show a heterogeneous phenotype and segregate into distinct subsets expressing IL-4, IL-13, activation, or degranulation markers. We find that several innate stimuli including epithelial derived inflammatory cytokines (IL-33, IL-18, TSLP, and GM-CSF), growth factors (IL-3, IL-7, TGFβ, and VEGF), eicosanoids, metabolites, TLR ligands, and type I IFN exert significant direct effects on basophils. Basophil activation mediated by distinct upstream signaling pathways is always sensitive to Syk and IκB kinases-specific inhibitors but not necessarily to NFAT, STAT5, adenylate cyclase, or c-fos/AP-1 inhibitors. Thus, basophils are activated by very diverse mediators, but their activation seem controlled by a core checkpoint involving Syk and IκB kinases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Basophil | interleukin 4 | interleukin 13 | Syk | inhibitor of kB kinases
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180189
作者单位Malaghan Institute of Medical Research, Victoria University, Wellington, 6242, New Zealand; INSERM UMR 1149, CNRS ERL 8252, Centre de recherche sur l’inflammation, Laboratoire d’excellence Inflamex, DHU Fire, Université de Paris, Paris, 75018, France
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Pellefigues C.,Mehta P.,Chappell S.,et al. Diverse innate stimuli activate basophils through pathways involving Syk and IκB kinases[J],2021,118(12).
APA Pellefigues C..,Mehta P..,Chappell S..,Yumnam B..,Old S..,...&Le Gros G..(2021).Diverse innate stimuli activate basophils through pathways involving Syk and IκB kinases.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA Pellefigues C.,et al."Diverse innate stimuli activate basophils through pathways involving Syk and IκB kinases".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).
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