ORIGINAL ARTICLE

Colony-stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma

Corresponding Author

Hyung-Geun Moon

[email protected]

orcid.org/0000-0003-3752-3035

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

Correspondence

Hyung-Geun Moon and Gye Young Park, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, 840 S. Wood St. CSB-920N, Chicago, IL 60612, USA.

Email: [email protected] (H-.G. M.); [email protected] (G. Y. P.)

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Seung-jae Kim,

Seung-jae Kim

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

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Myoung Kyu Lee,

Myoung Kyu Lee

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

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Homan Kang,

Homan Kang

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

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Hak Soo Choi,

Hak Soo Choi

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

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Anantha Harijith,

Anantha Harijith

Department of Pediatrics, University of Illinois at Chicago, IL, USA

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Jinhong Ren,

Jinhong Ren

Center for Biomolecular Science, College of Pharmacy, University of Illinois at Chicago, IL, USA

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Viswanathan Natarajan,

Viswanathan Natarajan

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

Department of Pharmacology, University of Illinois at Chicago, IL, USA

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John W. Christman,

John W. Christman

Section of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung, the Ohio State University, Columbus, OH, USA

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Steven J. Ackerman,

Steven J. Ackerman

Department of Pharmacology, University of Illinois at Chicago, IL, USA

Department of Biochemistry and Molecular Genetics, and Medicine, University of Illinois at Chicago, IL, USA

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Gye Young Park,

Corresponding Author

Gye Young Park

[email protected]

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

Correspondence

Hyung-Geun Moon and Gye Young Park, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, 840 S. Wood St. CSB-920N, Chicago, IL 60612, USA.

Email: [email protected] (H-.G. M.); [email protected] (G. Y. P.)

Search for more papers by this author

Hyung-Geun Moon,

Corresponding Author

Hyung-Geun Moon

[email protected]

orcid.org/0000-0003-3752-3035

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

Correspondence

Hyung-Geun Moon and Gye Young Park, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, 840 S. Wood St. CSB-920N, Chicago, IL 60612, USA.

Email: [email protected] (H-.G. M.); [email protected] (G. Y. P.)

Search for more papers by this author

Seung-jae Kim,

Seung-jae Kim

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

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Myoung Kyu Lee,

Myoung Kyu Lee

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

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Homan Kang,

Homan Kang

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

Search for more papers by this author

Hak Soo Choi,

Hak Soo Choi

Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

Search for more papers by this author

Anantha Harijith,

Anantha Harijith

Department of Pediatrics, University of Illinois at Chicago, IL, USA

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Jinhong Ren,

Jinhong Ren

Center for Biomolecular Science, College of Pharmacy, University of Illinois at Chicago, IL, USA

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Viswanathan Natarajan,

Viswanathan Natarajan

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

Department of Pharmacology, University of Illinois at Chicago, IL, USA

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John W. Christman,

John W. Christman

Section of Pulmonary, Critical Care, and Sleep Medicine, Davis Heart and Lung, the Ohio State University, Columbus, OH, USA

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Steven J. Ackerman,

Steven J. Ackerman

Department of Pharmacology, University of Illinois at Chicago, IL, USA

Department of Biochemistry and Molecular Genetics, and Medicine, University of Illinois at Chicago, IL, USA

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Gye Young Park,

Corresponding Author

Gye Young Park

[email protected]

Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA

Correspondence

Hyung-Geun Moon and Gye Young Park, Division of Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago, 840 S. Wood St. CSB-920N, Chicago, IL 60612, USA.

Email: [email protected] (H-.G. M.); [email protected] (G. Y. P.)

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First published: 06 August 2019

https://doi.org/10.1111/all.14011

Citations: 33

Hyung-Geun Moon and Gye Young Park contributed equally.

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Abstract

Background

A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation.

Objective

To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallergens.

Methods

We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe.

Results

Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction.

Conclusion

The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.

Graphical Abstract

Genetic manipulation or pharmacological inhibition of the CSF1-CSF1R signaling pathway suppresses allergen sensitization and lowers the production of allergen-specific serum IgE. Inhibition of the CSF1-CSF1R pathway reverses established chronic allergic inflammation and airway remodeling. Intranasal delivery of CSF1R inhibitor carrying nanoprobes has efficacy and shows favorable pharmacokinetics without significant adverse effects. CSF1, colony stimulating factor 1

CONFLICT OF INTEREST

HM and GYP have filed a provisional patent application related to the submitted manuscript.

Supporting Information

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Volume75, Issue2

February 2020

Pages 357-369

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