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A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma

Cellular & Molecular Immunology volume 15, pages 838–845 (2018)Cite this article

A Correction to this article was published on 23 May 2023

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Abstract

Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report here that genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulation of eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergic inflammation. The loss of PD-1H led to elevated production of both innate cytokines (IL-6, MCP-1 and TNFα) and Th2 cytokines (IL-5 and IL-13) in the lung, indicating a critical role of PD-1H in suppressing the production of airway inflammatory cytokines. In addition, the loss of PD-1H also impaired the expansion of systemic and pulmonary regulatory T cells during asthma induction. These findings support a critical role of intrinsic PD-1H in the regulation of inflammatory responses to allergens. Finally, we showed that treatment with a PD-1H agonistic monoclonal antibody reduced the severity of asthma, which was accompanied by suppressed lung inflammation. Our findings support PD-1H as a potential target and suggest a possible strategy for the treatment of allergic asthma in humans.

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Acknowledgements

This work is supported in part by the 985 project grant from Sun Yat-Sen University, Guangdong Province Innovative Research Program Project 2011Y035, PRC; National Institutes of Health grants P50 CA196530 and P30 CA016359; and an endowment from the United Technologies Corporation, USA.

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Authors and Affiliations

  1. Laboratory of Immunotherapy, Sun Yet-Sen University, Guangzhou, Guangdong, People’s Republic of China

    Huafeng Liu, Xin Li, Li Hu, Min Zhu, Bailin He, Liqun Luo & Lieping Chen

  2. Department of Immunobiology, Yale School of Medicine, Yale University, New Haven, 06511, CT, USA

    Lieping Chen

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  1. Huafeng Liu
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  3. Li Hu
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Contributions

HL and LC developed the concept, designed the experiments and wrote the manuscript. XL, LH and LL advised, and/or performed the experiments.

Corresponding author

Correspondence to Lieping Chen.

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Conflict of interest

LC serves as an advisor/board member for Pfizer, AstraZeneca, NextCure, GenomiCare and Vcanbio, and receives research support from Boehringer Ingelheim, Pfizer and NextCure. LC also serves as an uncompensated adjunct faculty member of Sun Yat-Sen University. The remaining authors declare no conflict of interest.

Additional information

The original online version of this article was revised: In the Acknowledgement section of this article, NIH grants numbered P50 CA196530 and P30 CA016359 were incorrectly attributed to author Lieping Chen and should not have been cited. The original article has been corrected.

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Liu, H., Li, X., Hu, L. et al. A crucial role of the PD-1H coinhibitory receptor in suppressing experimental asthma. Cell Mol Immunol 15, 838–845 (2018). https://doi.org/10.1038/cmi.2017.16

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