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Anti-ST2 Nanoparticle Alleviates Lung Inflammation by Targeting ILC2s-CD4+T Response

Authors Wu Y, Shi W, Wang H, Yue J, Mao Y, Zhou W, Kong X, Guo Q, Zhang L, Xu P, Wang Y

Received 10 July 2020

Accepted for publication 4 November 2020

Published 3 December 2020 Volume 2020:15 Pages 9745—9758


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster

Yumin Wu,1,* Weifeng Shi,1,* Honghai Wang,2,* Jiawei Yue,2 Yijie Mao,1 Wei Zhou,1 Xinagmin Kong,1 Qiqiong Guo,1 Lirong Zhang,1 Pengxiao Xu,1 Yuyue Wang1

1Department of Laboratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China; 2Department of Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China

*These authors contributed equally to this work

Correspondence:Yuyue Wang
The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, People’s Republic of China

Background: Asthma has been regarded as an inflammatory disease, and group 2 innate lymphoid cells (ILC2s) are implicated in asthma pathogenesis. However, no strategy is available to block ILC2s function. Efficiency is also limited due to the use of systemic or subcutaneous routes of administration. The purpose of this study was to investigate the effects of nanoparticles targeting suppression of tumorigenicity 2 (ST2), which is the ILC2 receptor, to alleviate lung inflammation in the murine model of asthma.
Methods: The ultra-small SPIO nanoparticles were firstly synthesized, OVA-induced mice were administered by anti-ST2-conjugated nanoparticles. The inflammatory degree of the lung was investigated by H&E. The percentages of ILC2s and CD4+T cells in bronchoalveolar lavage fluid (BALF) and lung tissue were determined by FACS. Th2-cytokine and OVA-IgE levels were detected by real-time PCR and ELISA, respectively.
Results: Treatment with anti-ST2-conjugated nanoparticles significantly alleviated airway inflammation, IL-33 and IL-13 levels and the percentage of CD4+T cells. The percentage of ILC2s was increased, whereas the levels of IL-13 and IL-5 expressed by ILC2s were reduced.
Conclusion: In the present study, we demonstrated that anti-ST2-conjugated nanoparticles can efficiently control lung inflammation in OVA-induced mice by reducing the ability of ILC2s to produce IL-5 and IL-13, thereby reducing CD4+T cells. Our study also demonstrated that the nanoparticle delivery system could improve the performance of anti-ST2, which may be used as a strategic tool to expand the current drug market.

Keywords: anti-ST2, asthma, group 2 innate lymphoid cells, (ILC2s), CD4+T cells, nanoparticle

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