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核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

Nasal anti-CD3 monoclonal antibody ameliorates traumatic brain injury, enhances microglial phagocytosis and reduces neuroinflammation via IL-10-dependent T-microglia crosstalk.

作者信息

Izzy Saef, Yahya Taha, Albastaki Omar, Abou-El-Hassan Hadi, Aronchik Michael, Cao Tian, De Oliveira Marilia Garcia, Lu Kuan-Jung, Moreira Thais G, da Silva Patrick, Boucher Masen L, Beauchamp Leah C, S LeServe Danielle, Brandao Wesley Nogueira, Carolina Durão Ana, Lanser Toby, Montini Federico, Lee Joon-Hyuk, Bernstock Joshua D, Kaul Megha, Pasquarelli-do-Nascimento Gabriel, Chopra Kusha, Krishnan Rajesh, Mannix Rebekah, Rezende Rafael M, Quintana Francisco J, Butovsky Oleg, Weiner Howard L

机构信息

Immunology of Brain Injury Program, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.

Ann Romney Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Nat Neurosci. 2025 Mar;28(3):499-516. doi: 10.1038/s41593-025-01877-7. Epub 2025 Feb 27.

DOI:10.1038/s41593-025-01877-7
PMID:40016353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11893472/
Abstract

Neuroinflammation plays a crucial role in traumatic brain injury (TBI), contributing to both damage and recovery, yet no effective therapy exists to mitigate central nervous system (CNS) injury and promote recovery after TBI. In the present study, we found that nasal administration of an anti-CD3 monoclonal antibody ameliorated CNS damage and behavioral deficits in a mouse model of contusional TBI. Nasal anti-CD3 induced a population of interleukin (IL)-10-producing regulatory T cells (T cells) that migrated to the brain and closely contacted microglia. T cells directly reduced chronic microglia inflammation and regulated their phagocytic function in an IL-10-dependent manner. Blocking the IL-10 receptor globally or specifically on microglia in vivo abrogated the beneficial effects of nasal anti-CD3. However, the adoptive transfer of IL-10-producing T cells to TBI-injured mice restored these beneficial effects by enhancing microglial phagocytic capacity and reducing microglia-induced neuroinflammation. These findings suggest that nasal anti-CD3 represents a promising new therapeutic approach for treating TBI and potentially other forms of acute brain injury.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/53611f816478/41593_2025_1877_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/2a56b98e47d1/41593_2025_1877_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/620744fa8b9b/41593_2025_1877_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/a4d1d768f026/41593_2025_1877_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/98153758c616/41593_2025_1877_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/750c6bcf60ad/41593_2025_1877_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/7f1400da4dd5/41593_2025_1877_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/040388f45490/41593_2025_1877_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/80ed794c2541/41593_2025_1877_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/1459a8fc0f00/41593_2025_1877_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/1588c2cb45ef/41593_2025_1877_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/8550891411d8/41593_2025_1877_Fig11_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/8a0cb58ddda2/41593_2025_1877_Fig13_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/b53034034bc3/41593_2025_1877_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/e3aee1f405d3/41593_2025_1877_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/53611f816478/41593_2025_1877_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/2a56b98e47d1/41593_2025_1877_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/620744fa8b9b/41593_2025_1877_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/a4d1d768f026/41593_2025_1877_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/98153758c616/41593_2025_1877_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/750c6bcf60ad/41593_2025_1877_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/7f1400da4dd5/41593_2025_1877_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/040388f45490/41593_2025_1877_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/80ed794c2541/41593_2025_1877_Fig8_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/1459a8fc0f00/41593_2025_1877_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/1588c2cb45ef/41593_2025_1877_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/8550891411d8/41593_2025_1877_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/e3520b9663ed/41593_2025_1877_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/8a0cb58ddda2/41593_2025_1877_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/9e125db97f39/41593_2025_1877_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/b53034034bc3/41593_2025_1877_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/e3aee1f405d3/41593_2025_1877_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9a/11893472/53611f816478/41593_2025_1877_Fig17_ESM.jpg

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引用本文的文献

[1]
T Cell Involvement in Neuroinflammation After Traumatic Brain Injury: Implications for Therapeutic Intervention.

CNS Neurosci Ther. 2025-8

[2]
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[3]
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[4]
An experimental study of the dual modulation of the colchicine-induced rat model of Alzheimer's disease by superparamagnetic iron oxide nanoparticles (SPIONs) and the soluble product of Dipylidium caninum adult worm.

PLoS One. 2025-6-3

[5]
Two routes to tamp down microglia in traumatic brain injury.

Nat Rev Drug Discov. 2025-5

本文引用的文献

[1]
Long-term risk of cardiovascular disease after traumatic brain injury: screening and prevention.

Lancet Neurol. 2023-10

[2]
Nasal administration of anti-CD3 monoclonal antibody ameliorates disease in a mouse model of Alzheimer's disease.

Proc Natl Acad Sci U S A. 2023-9-12

[3]
After cell death: the molecular machinery of efferocytosis.

Exp Mol Med. 2023-8

[4]
Defects in lysosomal function and lipid metabolism in human microglia harboring a TREM2 loss of function mutation.

Acta Neuropathol. 2023-6

[5]
Nasal administration of anti-CD3 mAb (Foralumab) downregulates and increases and expression in T cells in subjects with COVID-19.

Proc Natl Acad Sci U S A. 2023-3-14

[6]
Mitochondrial control of microglial phagocytosis by the translocator protein and hexokinase 2 in Alzheimer's disease.

Proc Natl Acad Sci U S A. 2023-2-21

[7]
The hallmark and crosstalk of immune cells after intracerebral hemorrhage: Immunotherapy perspectives.

Front Neurosci. 2023-1-12

[8]
CLEC16A interacts with retromer and TRIM27, and its loss impairs endosomal trafficking and neurodevelopment.

Hum Genet. 2023-3

[9]
T cells modulate the microglial response to brain ischemia.

Elife. 2022-12-13

[10]
Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects.

Front Immunol. 2022

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