4.5 Article

Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response

Journal

PEDIATRIC ALLERGY AND IMMUNOLOGY
Volume 32, Issue 1, Pages 51-59

Publisher

WILEY
DOI: 10.1111/pai.13317

Keywords

bronchiolitis; immune response; lipid mediators; recurrent wheezing; type 2 innate lymphoid cells (ILC2)

Funding

  1. FIS (Fondo de Investigacion SanitariaSpanish Health Research Fund) [PI15/00803, FI16/00036, PI15CIII/00028]
  2. FEDER Funds (Fondo Europeo de Desarrollo Regional)
  3. Alfonso X El Sabio University Grant: VIII Convocatoria Santander-UAX
  4. CIBER de Enfermedades Respiratorias (CIBERES), a Carlos III Institute of Health Initiative

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The study found that bronchiolitis patients have higher levels of innate lymphoid cells and related mRNA compared to recurrent wheezing patients. The levels of pro-inflammatory and immunomodulatory factors in the supernatant were similar between the two groups, but a significant difference was found in the ratio of prostaglandin E2 and cysteinyl leukotrienes C4.
Background: Recurrent wheezing (RW) is frequently developed in infants that have suffered bronchiolitis (BCH) during first months of life, but the immune mechanism underlying is not clear. The goal was to analyze the innate immune response that characterizes BCH and RW. Methods: Ninety-eight and seventy hospitalized infants with BCH or RW diagnosis, respectively, were included. Nasopharyngeal aspirate (NPA) was processed. Cellular pellet was employed to evaluate type 2 innate lymphoid cells (ILC2) by flow cytometry and mRNA expression assays by semi-quantitative real-time PCR (qRT-PCR). In supernatant, twenty-seven pro-inflammatory and immunomodulatory factors, as well as lipid mediators and nitrites, were evaluated by ELISA and Luminex. Results: Bronchiolitis patients showed higher ILC2 percentage compared with RW (P < .05). Also, ST2(+)/ILC2 percentage was higher in the BCH group than in the RW group (P < .01). TLR3, IL33, IFNG, IL10, and FLG mRNA levels were significantly increased in BCH vs RW (P < .05). In supernatant, no significant differences were reached, observing similar levels of parameters linked to vascular damage, monocyte activation, and fibroblast growth. Prostaglandin E2 and cysteinyl Ieukotrienes C4 were evaluated; a significant difference was only found in their ratio. Conclusion: Bronchiolitis is associated with elevated nasal percentage of ILC2. This cellular population could be the key element in the differential immune response between BCH and RW which share some mechanisms such us monocyte activation, vascular damage, and fibroblast repair. Lipid mediators could play a role in the evolution of the disease later in life through innate lymphoid cells.

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