PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis

Jielin Duan; Zhiwen Huang; Ying Jiang; Mo Xian; Wanjun Wang; Zhaowei Yang; Xu Shi; Nan Jia; Naijian Li; Bizhou Li; Zexuan Lian; Xiaoping Ning; Yubiao Guo; Haixiong Tang; Meihua Dong; Li He; Wenqing Yang; Renke Mo; Peiying Huang; Guan Yang; Ruchong Chen; LinLing Cheng; Jing Li

doi:10.1111/resp.70045

PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis

Jielin Duan (Co-first Author)
, Zhiwen Huang (Co-first Author)
, Ying Jiang
, Mo Xian
, Wanjun Wang
, Zhaowei Yang
, Xu Shi
, Nan Jia
, Naijian Li
, Bizhou Li
, Zexuan Lian
, Xiaoping Ning
, Yubiao Guo
, Haixiong Tang
, Meihua Dong
, Li He
, Wenqing Yang
, Renke Mo
, Peiying Huang
, Guan Yang

Ruchong Chen, LinLing Cheng^*, Jing Li^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

4 Citations (Scopus)

Abstract

Background and Objective: Myeloid-derived suppressor cells (MDSCs) participate in the progression of many diseases including chronic lung diseases. However, whether MDSCs are accumulated in the lung and how MDSCs orchestrate the pulmonary microenvironment in bronchiectasis remains unknown. Here, we aim to test a hypothesis that PMN-MDSCs are accumulated in the lung and play a role in creating an airway immunosuppressive milieu, thereby relating to clinical outcomes in bronchiectasis.
Methods: Flow cytometry and immunofluorescence staining were performed for analysing the frequencies and presence of PMN-MDSCs, LOX-1⁺ neutrophils, and ARG-1⁺ PMN-MDSCs in PBMCs, sputum, and lung tissues. T-cell proliferation assays were established for evaluating the immunosuppressive activities of PMN-MDSCs. RNA sequencing was performed to investigate the underlying mechanism of PMN-MDSCs-mediated immunosuppression. The relationship of PMN-MDSCs with the time to next exacerbation and treatment response to antibiotic therapy was analysed.
Results: PMN-MDSCs are accumulated in the lung and blood in bronchiectasis patients compared to healthy individuals. The majority of neutrophils in the lung of bronchiectasis patients are LOX-1⁺ PMN-MDSCs. Mechanistically, PMN-MDSCs suppress T cell proliferation via secreting high levels of the enzyme arginase-1 (ARG-1). Notably, the frequencies of PMN-MDSCs in sputum negatively correlate with the time to next exacerbation in bronchiectasis patients. Additionally, antibiotic therapy dramatically decreases PMN-MDSCs frequencies in the airway of bronchiectasis patients.
Conclusion: These findings suggest that PMN-MDSCs accumulate and establish an immunosuppressive microenvironment in the lung via ARG-1 in bronchiectasis, which is associated with clinical outcome and response to antibiotic treatment, highlighting a potential role of PMN-MDSCs in bronchiectasis progression.
© 2025 Asian Pacific Society of Respirology.

Original language	English
Pages (from-to)	715-725
Number of pages	11
Journal	Respirology
Volume	30
Issue number	8
Online published	4 May 2025
DOIs	https://doi.org/10.1111/resp.70045
Publication status	Published - Aug 2025

Funding

This work was supported by grants from the National Natural Science Foundation of China (82161138020, U1801286, 82201929), China Postdoctoral Science Foundation (2022M720906), Talent Development Foundation of the First Dongguan Affiliated Hospital of Guangdong Medical University (GCC2025008), Science and Technology Program of Guangzhou (202102010011), and Zhongnanshan Medical Foundation of Guangdong Province (ZNSA\u20102020003, ZNSA\u20102020013). Funding:

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

ARG-1
bronchiectasis
clinical outcome
neutrophils
PMN-MDSCs

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10.1111/resp.70045

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Duan, J., Huang, Z., Jiang, Y., Xian, M., Wang, W., Yang, Z., Shi, X., Jia, N., Li, N., Li, B., Lian, Z., Ning, X., Guo, Y., Tang, H., Dong, M., He, L., Yang, W., Mo, R., Huang, P., ... Li, J. (2025). PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis. Respirology, 30(8), 715-725. https://doi.org/10.1111/resp.70045

@article{d342879dd85f4086a06a24bdea1c3667,

title = "PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis",

abstract = "Background and Objective: Myeloid-derived suppressor cells (MDSCs) participate in the progression of many diseases including chronic lung diseases. However, whether MDSCs are accumulated in the lung and how MDSCs orchestrate the pulmonary microenvironment in bronchiectasis remains unknown. Here, we aim to test a hypothesis that PMN-MDSCs are accumulated in the lung and play a role in creating an airway immunosuppressive milieu, thereby relating to clinical outcomes in bronchiectasis. Methods: Flow cytometry and immunofluorescence staining were performed for analysing the frequencies and presence of PMN-MDSCs, LOX-1+ neutrophils, and ARG-1+ PMN-MDSCs in PBMCs, sputum, and lung tissues. T-cell proliferation assays were established for evaluating the immunosuppressive activities of PMN-MDSCs. RNA sequencing was performed to investigate the underlying mechanism of PMN-MDSCs-mediated immunosuppression. The relationship of PMN-MDSCs with the time to next exacerbation and treatment response to antibiotic therapy was analysed. Results: PMN-MDSCs are accumulated in the lung and blood in bronchiectasis patients compared to healthy individuals. The majority of neutrophils in the lung of bronchiectasis patients are LOX-1+ PMN-MDSCs. Mechanistically, PMN-MDSCs suppress T cell proliferation via secreting high levels of the enzyme arginase-1 (ARG-1). Notably, the frequencies of PMN-MDSCs in sputum negatively correlate with the time to next exacerbation in bronchiectasis patients. Additionally, antibiotic therapy dramatically decreases PMN-MDSCs frequencies in the airway of bronchiectasis patients. Conclusion: These findings suggest that PMN-MDSCs accumulate and establish an immunosuppressive microenvironment in the lung via ARG-1 in bronchiectasis, which is associated with clinical outcome and response to antibiotic treatment, highlighting a potential role of PMN-MDSCs in bronchiectasis progression. {\textcopyright} 2025 Asian Pacific Society of Respirology.",

keywords = "ARG-1, bronchiectasis, clinical outcome, neutrophils, PMN-MDSCs",

author = "Jielin Duan and Zhiwen Huang and Ying Jiang and Mo Xian and Wanjun Wang and Zhaowei Yang and Xu Shi and Nan Jia and Naijian Li and Bizhou Li and Zexuan Lian and Xiaoping Ning and Yubiao Guo and Haixiong Tang and Meihua Dong and Li He and Wenqing Yang and Renke Mo and Peiying Huang and Guan Yang and Ruchong Chen and LinLing Cheng and Jing Li",

year = "2025",

month = aug,

doi = "10.1111/resp.70045",

language = "English",

volume = "30",

pages = "715--725",

journal = "Respirology",

issn = "1323-7799",

publisher = "John Wiley \& Sons",

number = "8",

}

Duan, J, Huang, Z, Jiang, Y, Xian, M, Wang, W, Yang, Z, Shi, X, Jia, N, Li, N, Li, B, Lian, Z, Ning, X, Guo, Y, Tang, H, Dong, M, He, L, Yang, W, Mo, R, Huang, P, Yang, G, Chen, R, Cheng, L & Li, J 2025, 'PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis', Respirology, vol. 30, no. 8, pp. 715-725. https://doi.org/10.1111/resp.70045

PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis. / Duan, Jielin (Co-first Author); Huang, Zhiwen (Co-first Author); Jiang, Ying et al.
In: Respirology, Vol. 30, No. 8, 08.2025, p. 715-725.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis

AU - Duan, Jielin

AU - Huang, Zhiwen

AU - Jiang, Ying

AU - Xian, Mo

AU - Wang, Wanjun

AU - Yang, Zhaowei

AU - Shi, Xu

AU - Jia, Nan

AU - Li, Naijian

AU - Li, Bizhou

AU - Lian, Zexuan

AU - Ning, Xiaoping

AU - Guo, Yubiao

AU - Tang, Haixiong

AU - Dong, Meihua

AU - He, Li

AU - Yang, Wenqing

AU - Mo, Renke

AU - Huang, Peiying

AU - Yang, Guan

AU - Chen, Ruchong

AU - Cheng, LinLing

AU - Li, Jing

PY - 2025/8

Y1 - 2025/8

N2 - Background and Objective: Myeloid-derived suppressor cells (MDSCs) participate in the progression of many diseases including chronic lung diseases. However, whether MDSCs are accumulated in the lung and how MDSCs orchestrate the pulmonary microenvironment in bronchiectasis remains unknown. Here, we aim to test a hypothesis that PMN-MDSCs are accumulated in the lung and play a role in creating an airway immunosuppressive milieu, thereby relating to clinical outcomes in bronchiectasis. Methods: Flow cytometry and immunofluorescence staining were performed for analysing the frequencies and presence of PMN-MDSCs, LOX-1+ neutrophils, and ARG-1+ PMN-MDSCs in PBMCs, sputum, and lung tissues. T-cell proliferation assays were established for evaluating the immunosuppressive activities of PMN-MDSCs. RNA sequencing was performed to investigate the underlying mechanism of PMN-MDSCs-mediated immunosuppression. The relationship of PMN-MDSCs with the time to next exacerbation and treatment response to antibiotic therapy was analysed. Results: PMN-MDSCs are accumulated in the lung and blood in bronchiectasis patients compared to healthy individuals. The majority of neutrophils in the lung of bronchiectasis patients are LOX-1+ PMN-MDSCs. Mechanistically, PMN-MDSCs suppress T cell proliferation via secreting high levels of the enzyme arginase-1 (ARG-1). Notably, the frequencies of PMN-MDSCs in sputum negatively correlate with the time to next exacerbation in bronchiectasis patients. Additionally, antibiotic therapy dramatically decreases PMN-MDSCs frequencies in the airway of bronchiectasis patients. Conclusion: These findings suggest that PMN-MDSCs accumulate and establish an immunosuppressive microenvironment in the lung via ARG-1 in bronchiectasis, which is associated with clinical outcome and response to antibiotic treatment, highlighting a potential role of PMN-MDSCs in bronchiectasis progression. © 2025 Asian Pacific Society of Respirology.

AB - Background and Objective: Myeloid-derived suppressor cells (MDSCs) participate in the progression of many diseases including chronic lung diseases. However, whether MDSCs are accumulated in the lung and how MDSCs orchestrate the pulmonary microenvironment in bronchiectasis remains unknown. Here, we aim to test a hypothesis that PMN-MDSCs are accumulated in the lung and play a role in creating an airway immunosuppressive milieu, thereby relating to clinical outcomes in bronchiectasis. Methods: Flow cytometry and immunofluorescence staining were performed for analysing the frequencies and presence of PMN-MDSCs, LOX-1+ neutrophils, and ARG-1+ PMN-MDSCs in PBMCs, sputum, and lung tissues. T-cell proliferation assays were established for evaluating the immunosuppressive activities of PMN-MDSCs. RNA sequencing was performed to investigate the underlying mechanism of PMN-MDSCs-mediated immunosuppression. The relationship of PMN-MDSCs with the time to next exacerbation and treatment response to antibiotic therapy was analysed. Results: PMN-MDSCs are accumulated in the lung and blood in bronchiectasis patients compared to healthy individuals. The majority of neutrophils in the lung of bronchiectasis patients are LOX-1+ PMN-MDSCs. Mechanistically, PMN-MDSCs suppress T cell proliferation via secreting high levels of the enzyme arginase-1 (ARG-1). Notably, the frequencies of PMN-MDSCs in sputum negatively correlate with the time to next exacerbation in bronchiectasis patients. Additionally, antibiotic therapy dramatically decreases PMN-MDSCs frequencies in the airway of bronchiectasis patients. Conclusion: These findings suggest that PMN-MDSCs accumulate and establish an immunosuppressive microenvironment in the lung via ARG-1 in bronchiectasis, which is associated with clinical outcome and response to antibiotic treatment, highlighting a potential role of PMN-MDSCs in bronchiectasis progression. © 2025 Asian Pacific Society of Respirology.

KW - ARG-1

KW - bronchiectasis

KW - clinical outcome

KW - neutrophils

KW - PMN-MDSCs

UR - https://www.scopus.com/pages/publications/105004224112

UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-105004224112&origin=recordpage

U2 - 10.1111/resp.70045

DO - 10.1111/resp.70045

M3 - RGC 21 - Publication in refereed journal

SN - 1323-7799

VL - 30

SP - 715

EP - 725

JO - Respirology

JF - Respirology

IS - 8

ER -

PMN-MDSCs Orchestrate the Immunosuppressive Microenvironment in the Lung and Are Associated With Clinical Outcome in Bronchiectasis

Abstract

Funding

UN SDGs

Research Keywords

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