Allergic fungal rhinosinusitis linked to other hyper-IgE syndromes through defective TH17 responses.
J Allergy Clin Immunol
; 2024 Jul 18.
Article
en En
| MEDLINE
| ID: mdl-39032670
ABSTRACT
BACKGROUND:
In a gene expression analysis comparing sinus mucosa samples from allergic fungal rhinosinusitis (AFRS) patients with samples from non-AFRS chronic rhinosinusitis with nasal polyp (CRSwNP) patients, the antimicrobial peptide (AMP) histatin 1 (HTN1) was found to be the most differentially downregulated gene in AFRS.OBJECTIVE:
We sought to identify the molecular etiology of the downregulated expression of HTN1.METHODS:
We used RT-PCR to compare the expression of AMPs and a fungistasis assay to evaluate the antifungal activity of sinus secretions. Using flow cytometry, we characterized the presence of TH17/TH22 cells and signal transducer and activator of transcription (STAT) signaling from AFRS patients, non-AFRS CRSwNP patients, and healthy controls.RESULTS:
We confirmed decreased expression of AMPs in AFRS sinus mucosa with concordant decrease in antifungal activity in sinus secretions. IL-22 and IL-22-producing T cells were deficient within sinus mucosa of AFRS patients. In vitro studies demonstrated a defect in IL-6/STAT3 signaling critical for TH17/TH22 differentiation. Epithelial cells from AFRS patients could express AMPs when stimulated with exogenous IL-22/IL-17 and circulating TH17 cell abundance was normal.CONCLUSIONS:
Similar to other hyper-IgE syndromes, but distinct from CRSwNP, AFRS patients express a defect in STAT3 activation limited to IL-6-dependent STAT3 phosphorylation that is critical for TH17/TH22 differentiation. This defect leads to a local deficiency of IL-17/IL-22 cytokines and deficient AMP expression within diseased sinus mucosa of AFRS patients. Our findings support evaluation of therapeutic approaches that enhance airway AMP production in AFRS.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2024
Tipo del documento:
Article