The IL-17F/IL17RC axis: an emerging actor driving pathogenic responses in ABPA

Author:

Gianluca Vascelli (IT)

Abstract:

Background:
Allergic bronchopulmonary Aspergillosis (ABPA) has been associated with lung disease severity in children with cystic fibrosis (CF). However, connections between airway inflammation, lung function impairment and release of immunoglobulins (Ig),remain poorly understood. By understanding how the cytokine pattern may affect Ig subclasses, we may identify not only the induction of non-beneficial IgE responses but also how cytokines may induce anti-fungal IgG subclasses with known anti-inflammatory role, also acting as a non-anaphylactic or ‘blocking immunoglobulin’ against non-beneficial IgE responses.
Objectives:

To understand the kinetics and determine the titers of the human antibody repertoires (IgG subclasses and IgE) against Aspergillus in the five stages of ABPA and to identify different cytokine patterns, that are known to correlate with Ig enhancement and disease severity and remission.

Methods:
We exposed polarized human bronchial epithelial cells (HBE) to cytokines to understand how immune microenvironment may affect the local inflammation. In addition, whole blood samples, serum samples and pharingeal aspirate were collected from CF and CF/ABPA patients and frozen immediately. ABPA was diagnosed using clinical symptoms (presence of epi- sodic bronchial obstructions or typical radiographic features). Among the diagnostic tests: the total IgE, specific IgE anti-Aspergillus fumigatus, and the prick test. Results obtained were validated in the ABPA mouse model, where we investigated which is the cytokine pattern able to shape the protective or non-protective antifungal Ig subclass.

Results:
Preliminary results show that that IL- 17F stimulation pivotally induced IL-5, IL-13 and IL-25, and upregulated mRNA of Muc5a, Eotaxin and Il-33 on HBE cells. IL-17F was also able to increase the protein expression of IL-17RC. These findings extend to humans the importance of the IL-17F–IL-17RC axis in the epithelial compartment. Here, we confirmed that CF HBE cells express higher levels of IL-33 accordingly to previous studies and higher levels of IL-17F in the sputum of CF patients compared to healthy individuals. More importantly, IL-17F levels negatively correlated with FEV1% and positively correlated with specific IgE against Aspergillus.

Abstract Number: 57

Conference Year: 2024

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