The CNS lymphatic system modulates the adaptive neuro-immune response in the perilesional cortex in a mouse model of traumatic brain injury
| Autor: | Sara Wojciechowski, Jari Koistinaho, Barbara Galbardi, Salli Antila, Francesco Noé, Meike Hedwig Keuters, Maria Vihma |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Pathology medicine.medical_specialty business.industry Traumatic brain injury Spleen T lymphocyte medicine.disease Lesion 03 medical and health sciences 0302 clinical medicine Lymphatic system medicine.anatomical_structure Immune system medicine Cytotoxic T cell medicine.symptom business 030217 neurology & neurosurgery CD8 030304 developmental biology |
| DOI: | 10.1101/821645 |
| Popis: | RationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous systems. The role of mLVs in modulating the neuro-immune response following a brain injury, however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after traumatic brain injury (TBI), suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified the subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of immune response in the brain after TBI.MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, implying that mLVs are important in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate with alterations in peripheral circulating T cells, as assessed one month after injury induction.ConclusionsOur data support the hypothesis that mLVs are pivotal for a proper and specific neuro-immune response after TBI, which is principally mediated by the resident memory CD8+ T cells. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|