• Transl Res · Oct 2024

    Single-cell RNA sequencing reveals the MIF/ACKR3 receptor-ligand interaction between neutrophils and nucleus pulposus cells in intervertebral disc degeneration.

    • Tao-Lan Zhang, Wen-Kang Chen, Xian-Peng Huang, Bo-Wen Zheng, Peng-Fei Wu, Bo-Yv Zheng, Ling-Xiang Jiang, David Escobar, Jing Li, Guo-Hua Lv, Wei Huang, Hong Zhou, Zhun Xu, and Ming-Xiang Zou.
    • Department of Pharmacy, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China.
    • Transl Res. 2024 Oct 1; 272: 1181-18.

    ObjectivesTo unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD).MethodsSingle-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo.ResultsWe sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors.ConclusionsThese data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.Copyright © 2024 Elsevier Inc. All rights reserved.

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