Next-Generation Neuroimmunology: New Technologies to Understand Central Nervous System Autoimmunity

• Published in: Trends in immunology Vol. 41; no. 4; pp. 341 - 354
• Main Authors: Meyer zu Hörste, Gerd, Gross, Catharina C., Klotz, Luisa, Schwab, Nicholas, Wiendl, Heinz
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2020; Elsevier Limited
• Subjects: Allergy and Immunology; Animal models; Animals; Antibodies; Antigens; Aquaporins; Autoimmune diseases; Autoimmunity; Autoimmunity - immunology; Brain research; Central nervous system; Central Nervous System - immunology; Cerebrospinal fluid; Disease; Encephalitis; Flow cytometry; Humans; Immune System Diseases - immunology; Immunologic Techniques; Immunology; Lymphocytes; Nervous system; Nervous System Diseases - immunology; Neuroimmunology; Neuroimmunomodulation - immunology; Parenchyma; Pathogenesis; Patients; T cell receptors; Therapeutic applications; Translation
• ISSN: 1471-4906; 1471-4981; 1471-4981
• DOI: 10.1016/j.it.2020.02.005

Understanding neuroimmunological disorders is essential for developing new diagnostic and therapeutic strategies. Rodent models have provided valuable insights, but are sometimes equated with their human counterparts. Here, we summarize how novel technologies may enable an improved human-focused view of immune mechanisms. Recent studies have applied these new technologies to the brain parenchyma, its surrounding cerebrospinal fluid, and peripheral immune compartments. Therapeutic interventions have also facilitated translational understanding in a reverse way. However, with improved technology, access to patient samples remains a rate-limiting step in translational research. We anticipate that next-generation neuroimmunology is likely to integrate, in the immediate future, diverse technical tools for optimal diagnosis, prognosis, and treatment of neuroimmunological disorders. Autoimmune diseases of the nervous system, particularly multiple sclerosis (MS), are only partly mimicked by commonly used animal models such as experimental autoimmune encephalomyelitis (EAE).Translational studies in patients are mostly based on: autopsy or biopsy material, cerebrospinal fluid (CSF), or peripheral blood. Disease-specific findings considerably depend on the compartment being analyzed.The advent of various immunotherapies has significantly enhanced our knowledge of phase-specific immunopathological mechanisms in the field of neuroimmunology; we can further learn (immune)pathogenesis from successful and unsuccessful therapeutic interventions.MS is specifically associated with complex alterations of various immune cells and parenchymal cells, contributing to the view that changes in immune regulatory networks can initiate and perpetuate the disease.Comparative, unbiased, and multidimensional high-resolution approaches are needed (e.g., using single cell transcriptomics) to reveal key pathogenic signatures in a compartment-specific manner in human nervous system autoimmunity.Orphan diseases such as Rasmussen encephalitis (RE) and Susac syndrome (SuS) can serve as paradigmatic disease entities to dissect defined mechanisms in comparison with more prevalent disorders.