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1.
Neuron ; 111(14): 2155-2169.e9, 2023 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-37148871

RESUMO

Spinal cord injury (SCI) causes lifelong debilitating conditions. Previous works demonstrated the essential role of the immune system in recovery after SCI. Here, we explored the temporal changes of the response after SCI in young and aged mice in order to characterize multiple immune populations within the mammalian spinal cord. We revealed substantial infiltration of myeloid cells to the spinal cord in young animals, accompanied by changes in the activation state of microglia. In contrast, both processes were blunted in aged mice. Interestingly, we discovered the formation of meningeal lymphatic structures above the lesion site, and their role has not been examined after contusive injury. Our transcriptomic data predicted lymphangiogenic signaling between myeloid cells in the spinal cord and lymphatic endothelial cells (LECs) in the meninges after SCI. Together, our findings delineate how aging affects the immune response following SCI and highlight the participation of the spinal cord meninges in supporting vascular repair.


Assuntos
Células Endoteliais , Traumatismos da Medula Espinal , Camundongos , Animais , Células Endoteliais/patologia , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Microglia/patologia , Células Mieloides , Mamíferos
2.
Nat Neurosci ; 21(10): 1380-1391, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30224810

RESUMO

Neuroinflammatory diseases, such as multiple sclerosis, are characterized by invasion of the brain by autoreactive T cells. The mechanism for how T cells acquire their encephalitogenic phenotype and trigger disease remains, however, unclear. The existence of lymphatic vessels in the meninges indicates a relevant link between the CNS and peripheral immune system, perhaps affecting autoimmunity. Here we demonstrate that meningeal lymphatics fulfill two critical criteria: they assist in the drainage of cerebrospinal fluid components and enable immune cells to enter draining lymph nodes in a CCR7-dependent manner. Unlike other tissues, meningeal lymphatic endothelial cells do not undergo expansion during inflammation, and they express a unique transcriptional signature. Notably, the ablation of meningeal lymphatics diminishes pathology and reduces the inflammatory response of brain-reactive T cells during an animal model of multiple sclerosis. Our findings demonstrate that meningeal lymphatics govern inflammatory processes and immune surveillance of the CNS and pose a valuable target for therapeutic intervention.


Assuntos
Encefalite/patologia , Encefalite/fisiopatologia , Vasos Linfáticos/fisiologia , Meninges/patologia , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Sistema Nervoso Central/imunologia , Sistema Nervoso Central/patologia , Células Dendríticas/patologia , Modelos Animais de Doenças , Encefalite/induzido quimicamente , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Linfonodos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , MicroRNAs/metabolismo , Glicoproteína Mielina-Oligodendrócito/toxicidade , Fragmentos de Peptídeos/toxicidade , Fármacos Fotossensibilizantes/farmacologia , Receptores CCR7/deficiência , Receptores CCR7/genética , Baço/patologia , Linfócitos T/fisiologia , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
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