Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Τρίτη 29 Ιανουαρίου 2019

Blockade of Repulsive guidance molecule b (RGMb) inhibits allergen-induced airways disease

Publication date: Available online 29 January 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Sanhong Yu, Krystle M. Leung, Hye-Young Kim, Sarah E. Umetsu, Yanping Xiao, Lee A. Albacker, Hyun-Jun Lee, Dale T. Umetsu, Gordon J. Freeman, Rosemarie H. DeKruyff

Abstract
Background

Allergic asthma causes morbidity in many individuals and novel precision-directed treatments would be valuable.

Objective

To examine the role of a novel innate molecule, repulsive guidance molecule b (RGMb), in murine models of allergic asthma.

Methods

In models of allergic asthma using OVA or cockroach allergen, mice were treated with anti-RGMb or control mAb and examined for airway inflammation and airway hyperreactivity (AHR), a cardinal feature of asthma. The mechanisms by which RGMb causes airways disease were also examined.

Results

We found that blockade of RGMb by treatment with anti-RGMb mAb effectively blocked the development of airway inflammation and AHR. Importantly, blockade of RGMb completely blocked the development of airway inflammation and AHR, even if treatment occurred only during the challenge (effector) phase. IL-25 played an important role in these models of asthma, since IL-25 receptor deficient mice failed to develop disease. RGMb was expressed primarily by innate cells in the lungs, including bronchial epithelial cells (known producers of IL-25), activated eosinophils and interstitial macrophages, which in the inflamed lung expressed the IL-25 receptor and produced IL-5 and IL-13. We also found that NEO1, the canonical receptor for RGMb, was expressed by interstitial macrophages and bronchial epithelial cells in the inflamed lung, suggesting that an innate RGMb-NEO1 axis might modulate allergic asthma.

Conclusions

These results demonstrate an important role for a novel innate pathway in regulating type 2 inflammation in allergic asthma, involving RGMb and RGMb-expressing cells such as interstitial macrophages and bronchial epithelial cells. Moreover, targeting this previously unappreciated innate pathway might provide an important treatment option for allergic asthma.

Graphical abstract

Graphical abstract for this article



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