Defining bronchial asthma with phosphoinositide 3-kinase delta activation: Towards endotype-driven management

Jae Seok Jeong, Jong Seung Kim, So Ri Kim, Yong Chul Lee

Research output: Contribution to journalReview article

Abstract

Phosphoinositide 3-kinase (PI3K) pathways play a critical role in orchestrating the chronic inflammation and the structural changes of the airways in patients with asthma. Recently, a great deal of progress has been made in developing selective and effective PI3K-targeted therapies on the basis of a vast amount of studies on the roles of specific PI3K isoforms and fine-tuned modulators of PI3Ks in a particular disease context. In particular, the pivotal roles of delta isoform of class I PI3Ks (PI3K-δ) in CD4-positive type 2 helper T cells-dominant disorders such as asthma have been consistently reported since the early investigations. Furthermore, there has been great advancement in our knowledge of the implications of PI3K-δ in various facets of allergic inflammation. This has involved the airway epithelial interface, adaptive T and B cells, potent effector cells (eosinophils and neutrophils), and, more recently, subcellular organelles (endoplasmic reticulum and mitochondria) and cytoplasmic innate immune receptors such as NLRP3 inflammasome, all of which make this PI3K isoform an important druggable target for treating asthma. Defining subpopulations of asthma patients with PI3K-δ activation, namely PI3K-δ-driven asthma endotype, may therefore provide us with a novel framework for the treatment of the disease, particularly for corticosteroid-resistant severe form, an important unresolved aspect of the current asthma management. In this review, we specifically summarize the recent advancement of our knowledge on the critical roles of PI3K-δ in the pathogenesis of bronchial asthma.

Original languageEnglish
Article number3525
JournalInternational journal of molecular sciences
Volume20
Issue number14
DOIs
Publication statusPublished - 2019 Jul 2

Fingerprint

asthma
1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Phosphotransferases
Asthma
Chemical activation
activation
Mitochondria
T-cells
Modulators
Cells
Protein Isoforms
Phosphatidylinositol 3-Kinases
eosinophils
corticosteroids
neutrophils
effectors
endoplasmic reticulum
pathogenesis
organelles

Keywords

  • bronchial asthma
  • endotype
  • phosphoinositide 3-kinase delta
  • precision medicine

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Defining bronchial asthma with phosphoinositide 3-kinase delta activation : Towards endotype-driven management. / Jeong, Jae Seok; Kim, Jong Seung; Kim, So Ri; Lee, Yong Chul.

In: International journal of molecular sciences, Vol. 20, No. 14, 3525, 02.07.2019.

Research output: Contribution to journalReview article

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