Latorre Group - Human Neuroimmunology

Research | Publications | Group Members | Open Positions

Our research focuses on the study of human self-reactive T cells in immune-mediated neurological diseases with the aim to gain insights into the fundamental biological processes involved in human autoimmune responses and then translate those findings into biomedical applications.

Human autoimmune diseases are a group of heterogeneous and complex disorders that affect up to approximately 10% of the population, thus representing a significant public health threat. Recent observations suggest that many neurological disorders, including diseases of the peripheral nervous system as well as brain-related disorders such as neurodegenerative diseases, epilepsy, and neuropsychiatric disorders may have an autoimmune origin. Despite enormous research effort, the underlying immune-mediated mechanisms are far from clear and the development of effective treatments is still a big medical challenge for most human autoimmune diseases. Notably, understanding how immune responses may influence the establishment and/or progression of most human neurological disorders remains elusive.

We have established an extremely sensitive experimental approach, based on the combination of in vitro cell-based screenings, flow cytometry analysis, generation of single cell clones and deep T cell receptor (TCR) sequencing, that is particularly suitable to isolate and characterize rare self-reactive T cells from the blood and cerebrospinal fluid (CSF) of patients and healthy donors. Recently, this tool allowed us to provide the first solid evidence of the autoimmune aetiology of narcolepsy (NT), a rare chronic sleep neurological disorder and to prompt new studies with major translational implications to the clinics (external pagesee nature paper).

Taking advantage of this newly developed methodology in combination with ex-vivo tetramer staining and single cell RNA sequencing (scRNAseq), we are currently implementing new workflows to provide an unbiased in-depth characterization of phenotype, frequency and TCR repertoire of self-reactive T cells as well as define the antigenic repertoire targeted by these cells in patients suffering from various neurological disorders.

Overall, our research goal is to increase our knowledge on basic aspects of human T cell biology in health and autoimmunity, with resulting impact for biomedical and clinical applications, including the development of new diagnostic and prognostic tools as well as of more effective and personalized therapeutic interventions.

Related articles

Nature paper "Autoreactive T cells target peripheral nerves in Guillain–Barré syndrome" announced on ETH News.
Read the interview with Daniela Latorre about her pioneering work on sleep disorders on ETH News
Daniela's research was also presented by PerkinElmer in a 
external pageSpotlight Research Interview.

 

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