Targeted nuclear degranulation of neutrophils promotes the progression of pneumonia in ulcerative colitis

Abstract

Background: Both intestinal and pulmonary systems are parts of the mucosal immune system, comprising ∼80% of all immune cells. These immune cells migrate or are transported between various mucosal tissues to maintain tissue homeostasis.

Methods: In this study, we isolated neutrophils from the peripheral blood of patients and utilized immunofluorescence, flow cytometry, and Western blotting to confirm the incidence of “nucleus-directed degranulation” in vitro. Subsequently, we conducted a precise analysis using arivis software. Furthermore, using the DSS mouse model of colitis and tissue clearing technologies, we validated the “targeted nuclear degranulation” of neutrophils and their migration to the lungs in an inflammatory intestinal environment.

Result: In this study, we found that among patients with ulcerative colitis, the migration of neutrophils with “targeted nuclear degranulation” from the intestinal mucosa to the lungs significantly exacerbates lung inflammation during pulmonary infections. Notably, patients with ulcerative colitis exhibited a higher abundance of neutrophils with targeted nuclear degranulation. Using DSS mice, we observed that neutrophils with targeted nuclear degranulation from the intestinal mucosa migrated to the lung and underwent activation during pulmonary infections. These neutrophils rapidly released a high amount of neutrophil extracellular traps to mediate the progression of lung inflammation. Alterations in the neutrophil cytoskeleton and its interaction with the nuclear membrane represent the primary mechanisms underlying targeted nuclear degranulation.

Conclusion: This study revealed that neutrophils accelerate lung inflammation progression in colitis, offering new insights and potential treatment targets for lung infections for patients with colitis.

Keywords

neutrophils / targeted nuclear degranulation / reverse migration / ulcerative colitis / pneumonia

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Grants No. 82270562, 82302800), China Postdoctoral Science Foundation (Grant No. 2024M751108), Tai Shan Young Scholar Foundation of Shandong Province (Grant No. tsqn202103190), Postdoctoral Fund of The Affiliated Hospital of Jining Medical University (Grant No. JYFY364862), Postdoctoral Innovation Program in Shandong Province (Grant No. SDCX-ZG-202400032), and Doctor Fund of The Affiliated Hospital of Jining Medical University (Grant No. 2022-BS-07). The authors would like to express their gratitude to EditSprings (https://www.editsprings.cn) for the expert linguistic services provided.

Author contributions

Yiming Shao (Project administration, Visualization, Writing—original draft), Qibing Zheng (Conceptualization, Visualization), Xiaobei Zhang (Data curation, Investigation, Project administration, Writing—review & editing), Ping Li (Data curation, Resources), Xingxin Gao (Formal analysis, Validation), Liming Zhang (Methodology), Jiahong Xu (Investigation, Writing—original draft), Lingchao Meng (Data curation, Resources), Yanyun Tian (Formal analysis, Software), Qinqin Zhang (Methodology, Validation), and Guangxi Zhou (Writing—original draft).

Supplementary data

Supplementary data are available at PCMEDI Journal online.

Conflict of interest

None declared. Data is available from the authors upon reasonable request.

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