Abstract
Introduction: Iron dyshomeostasis is implicated in the pathogenesis of asthma. Iron loading of airway cells & gene expression of the iron uptake protein, transferrin receptor (TFR)1, positively correlates with type-2 (T2) cytokine responses, which are associated with features of disease.
Methods: Anti-TFR1 (αTFR1) & -IL-13 (αIL-13) were intranasally administered to a murine model of house dust mite (HDM)-induced asthma. TFR1+ cell numbers T2 gene expression & lung function were assessed. Effects of IL-13 on TFR1 & matrix metalloprotease (MMP)9 responses in bone marrow derived macrophages (BMDM) were investigated.
Results: In HDM-induced asthma, αTFR1 reduces TFR1+ macrophages, but not TFR1+ epithelial cells. αTFR1 reduces airways inflammation, fibrosis, mucus secreting cells and airflow obstruction. αTFR1 has no effect on HDM-induced IL-13, but significantly suppresses MMP9 expression. IL-13 increases TFR1 expression in BMDMs & αIL-13 reduces TFR1+ macrophages in HDM-induced asthma. Significantly, the combination of IL-13 & HDM increases MMP9 expression in BMDMs.
Conclusion: We show a critical role for IL-13-mediated increases in TFR1 responses in the pathogenesis of asthma, highlighting the potential to target TFR1 in other diseases associated with altered iron metabolism such as COPD, idiopathic pulmonary fibrosis & cystic fibrosis.
Grant Support: University of Newcastle, HMRI
Footnotes
Cite this article as Eur Respir J 2022; 60: Suppl. 66, 4211.
This article was presented at the 2022 ERS International Congress, in session “-”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022
