ABSTRACT Distinct neutrophil populations arise during certain pathological conditions. The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related

systemic immune suppression remain unclear. In this study, using an experimental sepsis model that features immunosuppression, we identified a novel population of pathogenic CD200Rhigh

neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T (Treg) cells. Compared to their CD200Rlow

counterparts, sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction, with reduced chemotactic migration, superoxide anion production, and TNF-α production.

secondary infection challenge, leading to increased survival. Transcriptome analysis revealed that CD200Rhigh neutrophils expressed high levels of _Igf1_, which elicits the generation of

Treg cells, while the administration of an α-CD200R antibody inhibited Treg cell generation in a secondary infection model. Taken together, our findings revealed a novel CD200Rhigh

neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells. Access through your institution Buy or subscribe This is a preview

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PATHWAY MEDIATES NEUTROPHIL EXHAUSTION Article Open access 01 September 2020 DYSFUNCTION OF LOW-DENSITY NEUTROPHILS IN PERIPHERAL CIRCULATION IN PATIENTS WITH SEPSIS Article Open access 13

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2022;140:889–99. https://doi.org/10.1182/blood.2021014283. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by Basic Science

Research Program (NRF-2020M3A9D3038435, NRF-2017R1A5A1014560) and the Korea Initiative for Fostering the University of Research and Innovation Program (NRF-2020M3H1A1077095) through the

National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning and by a grant from the Korea Health Technology R&D Project through the Korea

Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C2004). AUTHOR INFORMATION Author notes * Geon Ho Bae

Present address: Division of Immunology, Boston Children’s Hospital, Boston, MA, USA AUTHORS AND AFFILIATIONS * Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419,

Republic of Korea Ye Seon Kim, Yu Sun Jeong, Geon Ho Bae, Ji Hyeon Kang & Yoe-Sik Bae * Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351,

Republic of Korea Mingyu Lee & Yoe-Sik Bae * Palo Alto Veterans Institute for Research, Veterans Affairs Hospital, Palo Alto, CA, 94304, USA Brian A. Zabel Authors * Ye Seon Kim View

author publications You can also search for this author inPubMed Google Scholar * Yu Sun Jeong View author publications You can also search for this author inPubMed Google Scholar * Geon Ho

Bae View author publications You can also search for this author inPubMed Google Scholar * Ji Hyeon Kang View author publications You can also search for this author inPubMed Google Scholar

* Mingyu Lee View author publications You can also search for this author inPubMed Google Scholar * Brian A. Zabel View author publications You can also search for this author inPubMed 

Google Scholar * Yoe-Sik Bae View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Y.K. designed and performed the research, analyzed the data,

and wrote the paper. Y.J. designed and performed the research, analyzed data, and wrote the paper. G.B. designed the experiments and analyzed the data. J.K. performed the research and

analyzed the data. M.L. designed the experiments and analyzed the data. B.A.Z. wrote the paper. Y.B. designed the research and wrote the paper. CORRESPONDING AUTHOR Correspondence to Yoe-Sik

Bae. ETHICS DECLARATIONS COMPETING INTERESTS YSK, YSJ, and YSB have filed a patent related to this work. The other authors declare no competing interests. SUPPLEMENTARY INFORMATION

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law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Kim, Y.S., Jeong, Y.S., Bae, G.H. _et al._ CD200Rhigh neutrophils with dysfunctional autophagy establish systemic

immunosuppression by increasing regulatory T cells. _Cell Mol Immunol_ 21, 349–361 (2024). https://doi.org/10.1038/s41423-024-01136-y Download citation * Received: 24 April 2023 * Revised:

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Nature SharedIt content-sharing initiative KEYWORDS * Sepsis * Neutrophils * CD200R * Autophagy * IGF-1 * Regulatory T cells