RGD Reference Report - Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33. - Rat Genome Database

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Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33.

Authors: Castanhinha, Susana  Sherburn, Rebekah  Walker, Simone  Gupta, Atul  Bossley, Cara J  Buckley, James  Ullmann, Nicola  Grychtol, Ruth  Campbell, Gaynor  Maglione, Marco  Koo, Sergio  Fleming, Louise  Gregory, Lisa  Snelgrove, Robert J  Bush, Andrew  Lloyd, Clare M  Saglani, Sejal 
Citation: Castanhinha S, etal., J Allergy Clin Immunol. 2015 Aug;136(2):312-22.e7. doi: 10.1016/j.jaci.2015.01.016. Epub 2015 Mar 5.
RGD ID: 39938968
Pubmed: PMID:25746970   (View Abstract at PubMed)
PMCID: PMC4534777   (View Article at PubMed Central)
DOI: DOI:10.1016/j.jaci.2015.01.016   (Journal Full-text)


BACKGROUND: The mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored.
OBJECTIVE: We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33.
METHODS: Eighty-two children (median age, 11.7 years; 63% male) with severe therapy-resistant asthma were included. SAFS (n = 38) was defined as specific IgE or skin prick test response positivity to Aspergillus fumigatus, Alternaria alternata, or Cladosporium herbarum. Clinical features and airway immunopathology were assessed. Chronic exposure to house dust mite and A alternata were compared in a neonatal mouse model.
RESULTS: Children with SAFS had earlier symptom onset (0.5 vs 1.5 years, P = .006), higher total IgE levels (637 vs 177 IU/mL, P = .002), and nonfungal inhalant allergen-specific IgE. Significantly more children with SAFS were prescribed maintenance oral steroids (42% vs 14%, P = .02). SAFS was associated with higher airway IL-33 levels. In neonatal mice A alternata exposure induced higher serum IgE levels, pulmonary IL-33 levels, and IL-13(+) innate lymphoid cell (ILC) and TH2 cell numbers but similar airway hyperresponsiveness (AHR) compared with those after house dust mite exposure. Lung IL-33 levels, IL-13(+) ILC numbers, TH2 cell numbers, IL-13 levels, and AHR remained increased with inhaled budesonide during A alternata exposure, but all features were significantly reduced in ST2(-/-) mice lacking a functional receptor for IL-33.
CONCLUSION: Pediatric SAFS was associated with more oral steroid therapy and higher IL-33 levels. A alternata exposure resulted in increased IL-33-mediated ILC2 numbers, TH2 cell numbers, and steroid-resistant AHR. IL-33 might be a novel therapeutic target for SAFS.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL33Humanasthma severityIEP associated with fungal infectious diseaseRGD 
Il33Ratasthma severityISOIL33 (Homo sapiens)associated with fungal infectious diseaseRGD 
Il33Mouseasthma severityISOIL33 (Homo sapiens)associated with fungal infectious diseaseRGD 
IL33HumanFungal Lung Diseases  ISOIl33 (Mus musculus)protein:increased expression:lungRGD 
Il33RatFungal Lung Diseases  ISOIl33 (Mus musculus)protein:increased expression:lungRGD 
Il33MouseFungal Lung Diseases  IEP protein:increased expression:lungRGD 
IL1RL1Humanrespiratory allergy  ISOIl1rl1 (Mus musculus)associated with Fungal Lung DiseasesRGD 
Il1rl1Ratrespiratory allergy  ISOIl1rl1 (Mus musculus)associated with Fungal Lung DiseasesRGD 
Il1rl1Mouserespiratory allergy  IMP associated with Fungal Lung DiseasesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Mus musculus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Homo sapiens)
IL1RL1  (interleukin 1 receptor like 1)
IL33  (interleukin 33)


Additional Information