Single-Cell RNA Sequencing Reveals Transcriptional Landscape of Neutrophils and Highlights the Role of TREM-1 in EAE.

Autor:	Quan M; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China., Zhang H; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China., Han X; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China., Ba Y; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China., Cui X; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China., Bi Y; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China., Yi L; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China., Li B; From the Department of Neurology (M.Q., H.Z., L.Y., B.L.), The Second Hospital of Hebei Medical University; the Key Laboratory of Hebei Neurology, Hebei Medical University, Ministry of Education, (M.Q., H.Z., L.Y., B.L.); and the Key Laboratory of Neurology of Hebei Province, (M.Q., H.Z., L.Y., B.L.), Shijiazhuang, Hebei, China; Department of Neurology (X.H.), Zhongshan People's Hospital, China; OE Biotech Co. (Yongbing Ba), Ltd. Shanghai, China; and School of Basic Medicine (X.C., Yanwei Bi), Hebei Medical University, Shijiazhuang, China.
Jazyk:	angličtina
Zdroj:	Neurology(R) neuroimmunology & neuroinflammation [Neurol Neuroimmunol Neuroinflamm] 2024 Sep; Vol. 11 (5), pp. e200278. Date of Electronic Publication: 2024 Jul 02.
DOI:	10.1212/NXI.0000000000200278
Abstrakt:	Background and Objectives: Neutrophils, underestimated in multiple sclerosis (MS), are gaining increased attention for their significant functions in patients with MS and the experimental autoimmune encephalomyelitis (EAE) animal model. However, the precise role of neutrophils in cervical lymph nodes (CLNs), the primary CNS-draining lymph nodes where the autoimmune response is initiated during the progression of EAE, remains poorly understood. Methods: Applying single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive immune cell atlas of CLNs during development of EAE. Through this atlas, we concentrated on and uncovered the transcriptional landscape, phenotypic and functional heterogeneity of neutrophils, and their crosstalk with immune cells within CLNs in the neuroinflammatory processes in EAE. Results: Notably, we observed a substantial increase in the neutrophil population in EAE mice, with a particular emphasis on the significant rise within the CLNs. Neutrophils in CLNs were categorized into 3 subtypes, and we explored the specific roles and developmental trajectories of each distinct neutrophil subtype. Neutrophils were found to engage in extensive interactions with other immune cells, playing crucial roles in T-cell activation. Moreover, our findings highlighted the strong migratory ability of neutrophils to CLNs, partly regulated by triggering the receptor expressed on myeloid cells 1 (TREM-1). Inhibiting TREM1 with LR12 prevents neutrophil migration both in vivo and in vitro. In addition, in patients with MS, we confirmed an increase in peripheral neutrophils with an upregulation of TREM-1. Discussion: Our research provides a comprehensive and precise single-cell atlas of CLNs in EAE, highlighting the role of neutrophils in regulating the periphery immune response. In addition, TREM-1 emerged as an essential regulator of neutrophil migration to CLNs, holding promise as a potential therapeutic target in MS.
Databáze:	MEDLINE
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