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Pulmonary type-2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids

Prasad Nagakumar1,2,3, Franz Puttur1,3, Lisa G Gregory1

  • 1National Heart and Lung Institute, Imperial College London, London, UK.

The European Respiratory Journal
|June 6, 2019
PubMed

Insights

Children with severe therapy-resistant asthma (STRA) have distinct airway molecular phenotypes, with elevated type-2 cells. Systemic corticosteroids improved symptoms and reduced exacerbations by reducing innate lymphoid cells (ILCs).

Area of Science:

  • Pediatric Pulmonology
  • Immunology
  • Molecular Biology

Background:

  • Severe therapy-resistant asthma (STRA) and difficult asthma (DA) in children present challenges in management.
  • The distinct airway molecular phenotypes and the role of innate lymphoid cells (ILCs) in response to steroids in DA and STRA remain unclear.

Purpose of the Study:

  • To investigate the airway molecular phenotypes of children with DA and STRA.
  • To determine the role of innate lymphoid cells (ILCs) and their steroid responsiveness in these pediatric asthma subtypes.

Main Methods:

  • Immunophenotyping of sputum and blood ILCs and T-cells from children with STRA, DA, and controls.
  • Longitudinal analysis of leukocytes pre- and post-intramuscular triamcinolone in STRA patients.
  • In vitro assessment of ILC steroid responsiveness.

Main Results:

  • STRA patients exhibited higher airway eosinophils, type 2 T-helper (Th2) cells, and ILC2s compared to DA and controls.
  • Intramuscular triamcinolone and in vitro steroids reduced ILC2s and Th2 cells.
  • Systemic corticosteroids improved asthma symptoms and reduced exacerbations, despite persistent IL-17+ cells and eosinophils.

Conclusions:

  • Pediatric STRA and DA have distinct airway molecular phenotypes, with STRA characterized by elevated type-2 cells.
  • Systemic corticosteroids, unlike inhaled steroids, improve symptom control and reduce exacerbations by reducing functional ILC2s.
  • Persistent IL-17+ lymphoid cells and eosinophils suggest complex underlying mechanisms in STRA.

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