PMID- 38468459
OWN - NLM
STAT- MEDLINE
DCOM- 20240313
LR  - 20240513
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 30
IP  - 3
DP  - 2024 Mar
TI  - CD4(+) CD11b(+) T cells infiltrate and aggravate the traumatic brain injury 
      depending on brain-to-cervical lymph node signaling.
PG  - e14673
LID - 10.1111/cns.14673 [doi]
LID - e14673
AB  - AIM: We aim to identify the specific CD4(+) T-cell subtype influenced by 
      brain-to-CLN signaling and explore their role during the acute phase of traumatic 
      brain injury (TBI). METHOD: Cervical lymphadenectomy or cervical afferent 
      lymphatic ligation was performed before TBI. Cytokine array and western blot were 
      used to detect cytokines, while the motor function was assessed using mNss and 
      rotarod test. CD4(+) T-cell subtypes in blood, brain, and CLNs were analyzed with 
      Cytometry by time-of-flight analysis (CyTOF) or fluorescence-activated cell 
      sorting (FACS). Brain edema and volume changes were measured by 9.4T MRI. 
      Neuronal apoptosis was evaluated by terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: Cervical 
      lymphadenectomy and ligation of cervical lymphatic vessels resulted in a 
      decreased infiltration of CD4(+) T cells, specifically CD11b-positive CD4(+) T 
      cells, within the affected region. The population of CD4(+) CD11b(+) T cells 
      increased in ligated CLNs, accompanied by a decrease in the average fluorescence 
      intensity of sphingosine-1-phosphate receptor-1 (S1PR1) on these cells. 
      Administration of CD4(+) CD11b(+) T cells sorted from CLNs into the lateral 
      ventricle reversed the attenuated neurologic deficits, brain edema, and lesion 
      volume following cervical lymphadenectomy. CONCLUSION: The infiltration of CD4(+) 
      CD11b(+) T cells exacerbates secondary brain damage in TBI, and this process is 
      modulated by brain-to-CLN signaling.
CI  - (c) 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & 
      Sons Ltd.
FAU - Jiang, Weiwei
AU  - Jiang W
AUID- ORCID: 0009-0008-3131-5212
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Liu, Xuanhui
AU  - Liu X
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Chen, Yupeng
AU  - Chen Y
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Liu, Mingqi
AU  - Liu M
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Yuan, Jiangyuan
AU  - Yuan J
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Nie, Meng
AU  - Nie M
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Fan, Yibing
AU  - Fan Y
AD  - Department of Neurosurgery, Tianjin First Central Hospital, Tianjin, China.
FAU - Wu, Di
AU  - Wu D
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Qian, Yu
AU  - Qian Y
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Sha, Zhuang
AU  - Sha Z
AUID- ORCID: 0000-0002-8110-1481
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Dong, Shiying
AU  - Dong S
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Wu, Chenrui
AU  - Wu C
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Liu, Tao
AU  - Liu T
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Huang, Jinhao
AU  - Huang J
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Zhang, Jianning
AU  - Zhang J
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Gao, Chuang
AU  - Gao C
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
FAU - Jiang, Rongcai
AU  - Jiang R
AUID- ORCID: 0000-0002-9119-0115
AD  - Department of Neurosurgery, General Hospital of Tianjin Medical University, 
      Tianjin, China.
AD  - State Key Laboratory of Experimental Hematology, Tianjin, China.
AD  - Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neurorepair 
      and Regeneration in Central Nervous System, Tianjin Medical University General 
      Hospital, Ministry of Education, Tianjin, China.
LA  - eng
GR  - 82001323/National Natural Science Foundation of China/
GR  - 82071390/National Natural Science Foundation of China/
GR  - 82271394/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Cytokines)
SB  - IM
MH  - Humans
MH  - Animals
MH  - *Brain Edema/pathology
MH  - T-Lymphocytes
MH  - *Brain Injuries, Traumatic/pathology
MH  - Brain/pathology
MH  - Apoptosis
MH  - Cytokines
MH  - *Lymphatic Vessels/pathology
MH  - CD4-Positive T-Lymphocytes
MH  - Lymph Nodes/diagnostic imaging/pathology
MH  - Disease Models, Animal
PMC - PMC10928342
OTO - NOTNLM
OT  - CD4+ T cell
OT  - brain-to-cervical lymph node signaling
OT  - immunoregulation
OT  - traumatic brain injury
COIS- The authors declare that they have no competing interests.
EDAT- 2024/03/12 06:43
MHDA- 2024/03/13 06:46
PMCR- 2024/03/11
CRDT- 2024/03/12 02:33
PHST- 2023/12/28 00:00 [revised]
PHST- 2023/09/01 00:00 [received]
PHST- 2024/02/16 00:00 [accepted]
PHST- 2024/03/13 06:46 [medline]
PHST- 2024/03/12 06:43 [pubmed]
PHST- 2024/03/12 02:33 [entrez]
PHST- 2024/03/11 00:00 [pmc-release]
AID - CNS14673 [pii]
AID - 10.1111/cns.14673 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2024 Mar;30(3):e14673. doi: 10.1111/cns.14673.