Title :

IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

Author(s) :

Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Kelly, Elizabeth A B [Auteur]
Shen, Zhong-Jian [Auteur]
Johansson, Mats W [Auteur]
Malter, James S [Auteur]
Jarjour, Nizar N [Auteur]

Journal title :

Journal of Immunology

Abbreviated title :

J Immunol

Volume number :

195

Pages :

2529-39

Publication date :

2015-09-15

ISSN :

1550-6606

English keyword(s) :

Asthma
Cells, Cultured
Enzyme Activation
Eosinophilia
Eosinophils
Granulocyte-Macrophage Colony-Stimulating Factor
Humans
Hypersensitivity
Interleukin-3
Interleukin-5
Interleukin-5 Receptor alpha Subunit
Phosphorylation
RNA, Messenger
Ribosomal Protein S6
Ribosomal Protein S6 Kinases
Semaphorins
Signal Transduction

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a ...
Show more >IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-27T14:47:21Z
2024-03-16T08:43:29Z