Dunbar, Hazel and Hawthorne, Ian J. and Tunstead, Courteney and Armstrong, Michelle E. and Donnelly, Seamas C. and English, Karen (2023) Blockade of MIF biological activity ameliorates house dust mite‐induced allergic airway inflammation in humanized MIF mice. The FASEB Journal, 37 (8). ISSN 0892-6638

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Abstract

Macrophage migration inhibitory factor (MIF) expression is controlled by a functional promoter polymorphism, where the number of tetranucleotide repeats (CATTn) corresponds to the level of MIF expression. To examine the role of this polymorphism in a pre-clinical model of allergic asthma, novel humanized MIF mice with increasing CATT repeats (CATT5 and CATT7) were used to generate a physiologically relevant scale of airway inflammation following house dust mite (HDM) challenge. CATT7 mice expressing high levels of human MIF developed an aggressive asthma phenotype following HDM challenge with significantly elevated levels of immune cell infiltration, production of inflammatory mediators, goblet cell hyperplasia, subepithelial collagen deposition, and airway resistance compared to wild-type controls. Importantly the potent MIF inhibitor SCD-19 significantly mitigated the pathophysiology observed in CATT7 mice after HDM challenge, demonstrating the fundamental role of endogenous human MIF expression in the severity of airway inflammation in vivo. Up to now, there are limited reproducible in vivo models of asthma airway remodeling. Current asthma medications are focused on reducing the acute inflammatory response but have limited effects on airway remodeling. Here, we present a reproducible pre-clinical model that capitulates asthma airway remodeling and suggests that in addition to having pro-inflammatory effects MIF may play a role in driving airway remodeling.

Item Type:	Article
Keywords:	airway inflammation; airway remodeling; allergic asthma; house dust mite; macrophagemigration inhibitory factor; MIF; MIF inhibitors; severe asthma;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	18560
Identification Number:	https://doi.org/10.1096/fj.202300787R
Depositing User:	Karen English
Date Deposited:	21 May 2024 14:48
Journal or Publication Title:	The FASEB Journal
Publisher:	Wiley
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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