2. Academic Validation
  3. CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

CD300LF+ microglia impede the neuroinflammation following traumatic brain injury by inhibiting STING pathway

  • CNS Neurosci Ther. 2024 Jul;30(7):e14824. doi: 10.1111/cns.14824.
Zhichao Lu 1 2 3 4,  Zongheng Liu 5,  Chenxing Wang 1 2 3 4,  Rui Jiang 1 2 3 4,  Ziheng Wang 4 6,  Weiquan Liao 1 2 3 4,  Wei Wang 7,  Jianfeng Chen 8,  Xingjia Zhu 1 2 3 4,  Jingwei Zhao 9,  Qianqian Liu 1 2 3 4,  Yang Yang 10,  Peipei Gong 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
  • 2 Neuro-Microscopy and Minimally Invasive Translational Medicine Innovation Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 3 Jiangsu Medical Innovation Centre, Neurological Disease Diagnosis and Treatment Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 4 Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 5 Department of Neurosurgery, Zhejiang Provincial Hospital of Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
  • 6 Department of Biobank, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 7 Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
  • 8 Department of Orthopedics and Traumatology, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu, China.
  • 9 Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Research Institute of Biliary Tract Disease, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 10 Department of Neurosurgery, Wuxi Taihu Hosptial, Wuxi, China.
PMID: 38965803 DOI: 10.1111/cns.14824
Abstract

Introduction: The diversity in microglial phenotypes and functions following traumatic brain injury (TBI) is poorly characterized. The aim of this study was to explore precise targets for improving the prognosis of TBI patients from a microglial perspective.

Objectives: To assess whether the prognosis of TBI can be improved by modulating microglia function.

Results: In CD300LF-deficient mice, we observed an increase in glial cell proliferation, more extensive neuronal loss, and worsened neurological function post-TBI. Transcriptomic comparisons between CD300LF-positive and CD300LF-negative microglia illuminated that the neuroprotective role of CD300LF is principally mediated by the inhibition of the STING signaling pathway. In addition, this protective effect can be augmented using the STING pathway inhibitor C-176.

Conclusions: Our research indicates that CD300LF reduces neuroinflammation and promotes neurological recovery after TBI, and that microglia are integral to the protective effects of CD300LF in this context. In summary, our findings highlight CD300LF as a critical molecular regulator modulating the adverse actions of microglia following acute brain injury and propose a novel therapeutic approach to enhance outcomes for patients with TBI.

Keywords

CD300LF; STING; microglia; neuroinflammation; single‐cell RNA sequencing; traumatic brain injury.

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