Julie Cécile Caroline Ribot - IMM, University of Lisboa
Title: γδ T cells are the major source of IL-17 in the meninges and control brain cognitive functions
Abstract:
γδ T cells are known to populate multiple tissues, such as the skin, gut or lung, where they make major contributions to local physiology. Here we investigated whether γδ T cells could play a role in normal brain function, given that αβ T cells were recently shown to be involved in learning behavior of mice: whereas IFN-γ producing subsets were detrimental (1), their IL-4-producing counterparts played a precognitive role (2). We found that γδ T cells infiltrate the meningeal spaces from the brain of naïve C57/BL6 mice already at birth and persisted throughout life. Strikingly, at 1 week of age, meningeal γδ T cells differentiated into IL-17 producers, which seemingly depended on IL-1β. In fact, γδ T cells were the major source of IL-17, whereas αβ T cells mostly provided IFN-γ in situ. To test whether IL-17-producing γδ T cells influenced the cognitive performance of mice, we scored the behavior of TCRδ-/-, IL-17-/- and respective WT littermate control mice in classical paradigms assessing learning capacities. We observed that, contrary to WT controls, mice deficient for γδ T cells or IL-17 displayed impaired short-term/working memory in the Y maze paradigm, but a normal long-term spatial memory in the Morris water maze. To identify the underlying molecular mediators, we performed a proteomic-based analysis of the hippocampus and the pre-frontal cortex from IL-17-/- and WT mice. Interestingly, our results highlighted a reduced plasticity of the glutamatergic synapses of IL-17-/- animals, as confirmed by Long Term Potentiation (LTP) measurements. Furthermore, we found that IL-17 enhanced Brain Derived Neurotropic Factor (BDNF) production by glial cells, thus providing a key mechanistic link between meningeal γδ T cells and neurons. Altogether, our data demonstrate that γδ T cells regulate brain cognitive functions through a novel IL-17-dependent mechanism.
Title: γδ T cells are the major source of IL-17 in the meninges and control brain cognitive functions
Abstract:
γδ T cells are known to populate multiple tissues, such as the skin, gut or lung, where they make major contributions to local physiology. Here we investigated whether γδ T cells could play a role in normal brain function, given that αβ T cells were recently shown to be involved in learning behavior of mice: whereas IFN-γ producing subsets were detrimental (1), their IL-4-producing counterparts played a precognitive role (2). We found that γδ T cells infiltrate the meningeal spaces from the brain of naïve C57/BL6 mice already at birth and persisted throughout life. Strikingly, at 1 week of age, meningeal γδ T cells differentiated into IL-17 producers, which seemingly depended on IL-1β. In fact, γδ T cells were the major source of IL-17, whereas αβ T cells mostly provided IFN-γ in situ. To test whether IL-17-producing γδ T cells influenced the cognitive performance of mice, we scored the behavior of TCRδ-/-, IL-17-/- and respective WT littermate control mice in classical paradigms assessing learning capacities. We observed that, contrary to WT controls, mice deficient for γδ T cells or IL-17 displayed impaired short-term/working memory in the Y maze paradigm, but a normal long-term spatial memory in the Morris water maze. To identify the underlying molecular mediators, we performed a proteomic-based analysis of the hippocampus and the pre-frontal cortex from IL-17-/- and WT mice. Interestingly, our results highlighted a reduced plasticity of the glutamatergic synapses of IL-17-/- animals, as confirmed by Long Term Potentiation (LTP) measurements. Furthermore, we found that IL-17 enhanced Brain Derived Neurotropic Factor (BDNF) production by glial cells, thus providing a key mechanistic link between meningeal γδ T cells and neurons. Altogether, our data demonstrate that γδ T cells regulate brain cognitive functions through a novel IL-17-dependent mechanism.