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성균관대학교

Cell. Mol. Immunol., 05 February 2024 | https://doi.org/10.1038/s41423-024-01136-y CD200Rhigh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells

Ye Seon Kim ¹, Yu Sun Jeong¹, Geon Ho Bae ¹, Ji Hyeon Kang ¹, Mingyu Lee ², Brian A. Zabel ³ & Yoe-Sik Bae^{1 2 *}

¹Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea

²Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, 06351, Republic of Korea

³Palo Alto Veterans Institute for Research, Veterans Affairs Hospital, Palo Alto, CA, 94304, USA

^*Corresponding author: correspondence to Yoe-Sik Bae

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 CD200R^high neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T (T_reg) cells. Compared to their CD200R^low counterparts, sepsis-generated CD200R^high neutrophils exhibit impaired autophagy and dysfunction, with reduced chemotactic migration, superoxide anion production, and TNF-α production. Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis, and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R^high neutrophils. The administration of an α-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge, leading to increased survival. Transcriptome analysis revealed that CD200R^high neutrophils expressed high levels of Igf1, which elicits the generation of T_reg cells, while the administration of an α-CD200R antibody inhibited T_reg cell generation in a secondary infection model. Taken together, our findings revealed a novel CD200R^high neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating T_reg cells.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-05)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학

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