Substance P promotes immunotherapy efficacy for airway allergy

Yongjin Wu, MD; Yu Liu, PhD; Xinxin Wang, MS; Huazhen Liu, MS; Gaohui Wu, MD, PhD; Liteng Yang, MD, PhD; Li Guan, MD; Qinmiao Huang, MD, PhD; Xianhai Zeng, MD; Pingchang Yang, MD, PhD

World Allergy Organization Journal (Jan 2023)

Substance P promotes immunotherapy efficacy for airway allergy

Yongjin Wu, MD,
Yu Liu, PhD,
Xinxin Wang, MS,
Huazhen Liu, MS,
Gaohui Wu, MD, PhD,
Liteng Yang, MD, PhD,
Li Guan, MD,
Qinmiao Huang, MD, PhD,
Xianhai Zeng, MD,
Pingchang Yang, MD, PhD

Affiliations

Yongjin Wu, MD: Department of Allergy, Longgang ENT Hospital, Shenzhen Key Laboratory of ENT & Shenzhen ENT Institute, Shenzhen, China
Yu Liu, PhD: Departments of Respirology and Allergy, Third Affiliated Hospital, Shenzhen University, Shenzhen, China
Xinxin Wang, MS: Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China; Institute of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China; State Key Laboratory of Respiratory Diseases Shenzhen University Division, Shenzhen, China; Shenzhen Municipal Key Laboratory of Allergy & Immunology, Shenzhen, China; Guangdong Provincial Center for Standardized Allergen Engineering, Shenzhen, China
Huazhen Liu, MS: Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China; Institute of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China; State Key Laboratory of Respiratory Diseases Shenzhen University Division, Shenzhen, China; Shenzhen Municipal Key Laboratory of Allergy & Immunology, Shenzhen, China; Guangdong Provincial Center for Standardized Allergen Engineering, Shenzhen, China
Gaohui Wu, MD, PhD: Departments of Respirology and Allergy, Third Affiliated Hospital, Shenzhen University, Shenzhen, China
Liteng Yang, MD, PhD: Departments of Respirology and Allergy, Third Affiliated Hospital, Shenzhen University, Shenzhen, China
Li Guan, MD: Departments of Respirology and Allergy, Third Affiliated Hospital, Shenzhen University, Shenzhen, China
Qinmiao Huang, MD, PhD: Departments of Respirology and Allergy, Third Affiliated Hospital, Shenzhen University, Shenzhen, China; Corresponding author.
Xianhai Zeng, MD: Department of Allergy, Longgang ENT Hospital, Shenzhen Key Laboratory of ENT & Shenzhen ENT Institute, Shenzhen, China; Corresponding author. Department of Otolaryngology, Longgang E.N.T Hospital, Shenzhen, China.
Pingchang Yang, MD, PhD: Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China; Institute of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China; State Key Laboratory of Respiratory Diseases Shenzhen University Division, Shenzhen, China; Shenzhen Municipal Key Laboratory of Allergy & Immunology, Shenzhen, China; Guangdong Provincial Center for Standardized Allergen Engineering, Shenzhen, China; Corresponding author. Room A7-509, 1066 Xueyuan Blvd, Shenzhen, 518055, China.

Journal volume & issue: Vol. 16, no. 1
p. 100730

Abstract

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Background: Allergen-specific immunotherapy (AIT) has been employed in the treatment of allergic diseases for many years. However, the effectiveness of AIT requires improvement. Substance P (SP) can interact with immune cells, modulate immune cell activity, and regulate immune reaction. The purpose of this study is to use SP as an immune regulator to enhance the therapeutic efficacy of AIT. Methods: An established mouse model of the airway allergy disorder (AAD) was employed with ovalbumin as a specific antigen. The AAD response was evaluated through established procedures. AAD mice were treated with AIT employing SP as an immune regulator. Dendritic cells were isolated from the airway tissues by magnetic cell sorting, and were analyzed by RNA sequencing (RNAseq). Results: We observed that after sensitization with ovalbumin, mice exhibited AAD-like symptoms, serum specific IgE, and Th2 polarization. The presence of SP in the course of sensitization prevented the development of AAD. Treating mice with SP by nasal instillations induced IL-10, but not TGF-β, in dendritic cells of the airway tissues. The most differentially expressed genes (DEG) in the dendritic cells were those related to the IL-10 expression, including Il10, Tac1r, and Mtor. The gene ontology analysis showed that these DEGs mainly mapped to the tachykinin-PI3K-AKT-mTOR pathway. The addition of SP substantially enhanced the therapeutic efficacy of AIT for AAD by inducing antigen specific type 1 regulatory T cells (Tr1 cells). Conclusion: Acting as an immune regulator, SP promotes the therapeutic efficacy for AAD by inducing antigen specific Tr1 cells in the airway tissues.

Published in World Allergy Organization Journal

ISSN: 1939-4551 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: https://www.sciencedirect.com/journal/world-allergy-organization-journal

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