T Cells Specifically Targeted to Amyloid Plaques Enhance Plaque Clearance in a Mouse Model of Alzheimer's Disease

Patients with Alzheimer's disease (AD) exhibit substantial accumulation of amyloid-β (Aβ) plaques in the brain. Here, we examine whether Aβ vaccination can facilitate the migration of T lymphocytes to specifically target Aβ plaques and consequently enhance their removal. Using a new mouse model of AD, we show that immunization with Aβ, but not with the encephalitogenic proteolipid protein (PLP), results in the accumulation of T cells at Aβ plaques in the brain. Although both Aβ-reactive and PLP-reactive T cells have a similar phenotype of Th1 cells secreting primarily IFN-γ, the encephalitogenic T cells penetrated the spinal cord and caused experimental autoimmune encephalomyelitis (EAE), whereas Aβ T cells accumulated primarily at Aβ plaques in the brain but not the spinal cord and induced almost complete clearance of Aβ. Furthermore, while a single vaccination with Aβ resulted in upregulation of the phagocytic markers triggering receptors expressed on myeloid cells-2 (TREM2) and signal regulatory protein-β1 (SIRPβ1) in the brain, it caused downregulation of the proinflammatory cytokines TNF-α and IL-6. We thus suggest that Aβ deposits in the hippocampus area prioritize the targeting of Aβ-reactive but not PLP-reactive T cells upon vaccination. The stimulation of Aβ-reactive T cells at sites of Aβ plaques resulted in IFN-γ-induced chemotaxis of leukocytes and therapeutic clearance of Aβ

Социокультурные особенности динамики миграционных процессов в центральной Сибири (на материалах исследований в Красноярском крае в 2010–2014 гг.)

Socio-cultural peculiarities of migration processes in one of the largest regions of Siberia – the Krasnoyarsk Territory are studied in the research paper. The research is based on the data of the survey of the Krasnoyarsk Territory population, conducted by semi-structured interview method according to the methodology of “Sociocultural Portrait of the Territory” in 2010, 2012 and 2014. The dynamics of emotional attitude of the Territory residents in the context of their migratory moods and opinions on the quality of life in the Krasnoyarsk Territory, compared with other regions of Siberia, on the cultural aspects of attractiveness (and unattractiveness) of life in the Territory are revealed in the article. Increase in the negative attitude of the Krasnoyarsk Territory population to the arriving migrants of other nationalities, associated, mainly, with the cultural antagonism has been revealed. This sociocultural situation is becoming more vivid at the behavioral level. The assumption of possible violation of the traditionally existed in the region tradition of multiculturalism in the future is madeВ статье рассматриваются социокультурные особенности миграционных процессов в одном из крупнейших регионов Сибири – Красноярском крае. Работа опирается на данные опросов населения Красноярского края, проведённых методом формализованного интервью по методике «Социокультурный портрет региона» в 2010, 2012 и 2014 гг. Раскрыты динамика эмоционального отношения жителей края в контексте их миграционных настроений, мнения о качестве жизни в Красноярском крае по сравнению с другими регионами Сибири, о культурных аспектах привлекательности (и непривлекательности) жизни в данном регионе. Выявлено некоторое усиление негативного отношения населения Красноярского края к прибывающим мигрантам иных национальностей, связанное главным образом с культурным антагонизмом. Эта социокультурная ситуация всё более ярко проявляется на поведенческом уровне. Выдвигается предположение о возможном нарушении в будущем традиционно существовавшей в регионе традиции мультикультурност

Социокультурные особенности динамики миграционных процессов в центральной Сибири (на материалах исследований в Красноярском крае в 2010–2014 гг.)

Socio-cultural peculiarities of migration processes in one of the largest regions of Siberia – the Krasnoyarsk Territory are studied in the research paper. The research is based on the data of the survey of the Krasnoyarsk Territory population, conducted by semi-structured interview method according to the methodology of “Sociocultural Portrait of the Territory” in 2010, 2012 and 2014. The dynamics of emotional attitude of the Territory residents in the context of their migratory moods and opinions on the quality of life in the Krasnoyarsk Territory, compared with other regions of Siberia, on the cultural aspects of attractiveness (and unattractiveness) of life in the Territory are revealed in the article. Increase in the negative attitude of the Krasnoyarsk Territory population to the arriving migrants of other nationalities, associated, mainly, with the cultural antagonism has been revealed. This sociocultural situation is becoming more vivid at the behavioral level. The assumption of possible violation of the traditionally existed in the region tradition of multiculturalism in the future is madeВ статье рассматриваются социокультурные особенности миграционных процессов в одном из крупнейших регионов Сибири – Красноярском крае. Работа опирается на данные опросов населения Красноярского края, проведённых методом формализованного интервью по методике «Социокультурный портрет региона» в 2010, 2012 и 2014 гг. Раскрыты динамика эмоционального отношения жителей края в контексте их миграционных настроений, мнения о качестве жизни в Красноярском крае по сравнению с другими регионами Сибири, о культурных аспектах привлекательности (и непривлекательности) жизни в данном регионе. Выявлено некоторое усиление негативного отношения населения Красноярского края к прибывающим мигрантам иных национальностей, связанное главным образом с культурным антагонизмом. Эта социокультурная ситуация всё более ярко проявляется на поведенческом уровне. Выдвигается предположение о возможном нарушении в будущем традиционно существовавшей в регионе традиции мультикультурност

The Choroid Plexus Functions as a Niche for T-Cell Stimulation Within the Central Nervous System

The choroid plexus (CP) compartment in the ventricles of the brain comprises fenestrated vasculature and, therefore, it is permeable to blood-borne mediators of inflammation. Here, we explored whether T-cell activation in the CP plays a role in regulating central nervous system (CNS) inflammation. We show that CD4 T cells injected into the lateral ventricles adhere to the CP, transmigrate across its epithelium, and undergo antigen-specific activation and proliferation. This process is enhanced following peripheral immune stimulation and significantly impacts the immune signaling induced by the CP. Ex vivo studies demonstrate that T-cell harboring the CP through its apical surface is a chemokine- and adhesion molecule-dependent process. We suggest that, within the CNS, the CP serves an immunological niche, which rapidly responds to peripheral inflammation and, thereby, promotes two-way T-cell trafficking that impact adaptive immunity in the CNS

data_sheet_1_The Choroid Plexus Functions as a Niche for T-Cell Stimulation Within the Central Nervous System.PDF

<p>The choroid plexus (CP) compartment in the ventricles of the brain comprises fenestrated vasculature and, therefore, it is permeable to blood-borne mediators of inflammation. Here, we explored whether T-cell activation in the CP plays a role in regulating central nervous system (CNS) inflammation. We show that CD4 T cells injected into the lateral ventricles adhere to the CP, transmigrate across its epithelium, and undergo antigen-specific activation and proliferation. This process is enhanced following peripheral immune stimulation and significantly impacts the immune signaling induced by the CP. Ex vivo studies demonstrate that T-cell harboring the CP through its apical surface is a chemokine- and adhesion molecule-dependent process. We suggest that, within the CNS, the CP serves an immunological niche, which rapidly responds to peripheral inflammation and, thereby, promotes two-way T-cell trafficking that impact adaptive immunity in the CNS.</p

video_1_The Choroid Plexus Functions as a Niche for T-Cell Stimulation Within the Central Nervous System.avi

<p>The choroid plexus (CP) compartment in the ventricles of the brain comprises fenestrated vasculature and, therefore, it is permeable to blood-borne mediators of inflammation. Here, we explored whether T-cell activation in the CP plays a role in regulating central nervous system (CNS) inflammation. We show that CD4 T cells injected into the lateral ventricles adhere to the CP, transmigrate across its epithelium, and undergo antigen-specific activation and proliferation. This process is enhanced following peripheral immune stimulation and significantly impacts the immune signaling induced by the CP. Ex vivo studies demonstrate that T-cell harboring the CP through its apical surface is a chemokine- and adhesion molecule-dependent process. We suggest that, within the CNS, the CP serves an immunological niche, which rapidly responds to peripheral inflammation and, thereby, promotes two-way T-cell trafficking that impact adaptive immunity in the CNS.</p

La composición escrita (de 3 a 16 años)

Resumen tomado de la publicaciónSe presenta un recorrido que trata aspectos de la expresión o producción escrita, con la intención de fomentar el debate, a través de las reflexiones de diferentes autores, sobre el uso de la lengua y su dedáctica; y, por otro lado, mostrar mediante buenas prácticas, cómo se puede trabajar la lengua escrita a lo largo de la escolarización, desde los más pequeños a los mayores, trabajando con recetas de cocina, escribiendo cartas a compañeros de otros centros, inventando cuentos o creando textos literarios en los talleres.CataluñaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]