RESUMEN
Dendritic cells (DCs) are essential orchestrators of immune responses and represent potential targets for immunomodulation in autoimmune diseases. Human amniotic fluid secretome is abundant in immunoregulatory factors, with extracellular vesicles (EVs) being a significant component. However, the impact of these EVs on dendritic cells subsets remain unexplored. In this study, we investigated the interaction between highly purified dendritic cell subsets and EVs derived from amniotic fluid stem cell lines (HAFSC-EVs). Our results suggest that HAFSC-EVs are preferentially taken up by conventional dendritic cell type 2 (cDC2) through CD29 receptor-mediated internalization, resulting in a tolerogenic DC phenotype characterized by reduced expression and production of pro-inflammatory mediators. Furthermore, treatment of cDC2 cells with HAFSC-EVs in coculture systems resulted in a higher proportion of T cells expressing the regulatory T cell marker Foxp3 compared to vehicle-treated control cells. Moreover, transfer of HAFSC-EV-treated cDC2s into an EAE mouse model resulted in the suppression of autoimmune responses and clinical improvement. These results suggest that HAFSC-EVs may serve as a promising tool for reprogramming inflammatory cDC2s towards a tolerogenic phenotype and for controlling autoimmune responses in the central nervous system, representing a potential platform for the study of the effects of EVs in DC subsets.
Asunto(s)
Líquido Amniótico , Células Dendríticas , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental , Vesículas Extracelulares , Esclerosis Múltiple , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Ratones , Líquido Amniótico/citología , Líquido Amniótico/metabolismo , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/terapia , Encefalomielitis Autoinmune Experimental/metabolismo , Humanos , Esclerosis Múltiple/terapia , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Femenino , Células Madre/metabolismo , Células Madre/citología , Ratones Endogámicos C57BLRESUMEN
Epilepsy is a neurological disorder arising from anomalies of the electrical activity in the brain, affecting about 65 millions individuals worldwide. OBJECTIVE: This paper proposes a patient-specific approach for short-term prediction (i.e., within few minutes) of epileptic seizures. METHODS: We use noninvasive EEG data, since the aim is exploring the possibility of developing a noninvasive monitoring/control device for the prediction of seizures. Our approach is based on finding synchronization patterns in the EEG that allow to distinguish in real time preictal from interictal states. In practice, we develop easily computable functions over a graph model to capture the variations in the synchronization, and employ a classifier for identifying the preictal state. RESULTS: We compare two state-of-the-art classification algorithms and a simple and computationally inexpensive threshold-based classifier developed ad hoc. Results on publicly available scalp EEG database and on scalp data of the patients of the Unit of Neurology and Neurophysiology at University of Siena show that this simple and computationally viable processing is able to highlight the changes in synchronization when a seizure is approaching. CONCLUSION AND SIGNIFICANCE: The proposed approach, characterized by low computational requirements and by the use of noninvasive techniques, is a step toward the development of portable and wearable devices for real-life use.