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Publications

Journal Article Review Ahead of print

PubMed: 42934341 DOI: 10.1038/s41582-026-01272-1

Use of animal models to understand CNS neuroimmunology - guidance from the International Society for Neuroimmunology White Paper Task Force.

Nat Rev Neurol

Authors: Jennifer L Gommerman, Katerina Akassoglou, Sergio E Baranzini, Burkhard Becher, Fabienne Brilot, Gonçalo Castelo-Branco, Shannon E Dunn, Maryam Faiz, Alexander Flügel, Nader Ghasemlou, Erin M Gibson, Judith M Greer, Denis Gris, Cole A Harrington, Steffen Jung, Lorraine V Kalia, Thomas Korn, Gurumoorthy Krishnamoorthy, Roland S Liblau, Francesca Odoardi, Laura Piccio, Anne-Katrin Pröbstel, Francisco J Quintana, Valeria Ramaglia, Manu Rangachari, Olga L Rojas, Marc J Ruitenberg, Scott Russo, Dorothy P Schafer, Benjamin M Segal, Jana Vukovic, Chao Wang, Michael A Wheeler, Heinz Wiendl, V Wee Yong, Frauke Zipp, Veronique E Miron

Affiliations

  • Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
  • Gladstone Institute of Neurological Disease, San Francisco, CA, USA.
  • Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.
  • Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Kids Neuroscience Centre, Kids Research at the Children's Hospital at Westmead, The University of Sydney, Faculty of Medicine and Health, Sydney, New South Wales, Australia.
  • Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
  • Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
  • Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
  • Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
  • Institute for Neuroimmunology and Multiple Sclerosis Research, University Medical Center Göttingen, Göttingen, Germany.
  • Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
  • Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
  • UQ Centre for Clinical Research, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia.
  • Department of Pharmacology-Physiology, The University of Sherbrooke, Sherbrooke, Quebec, Canada.
  • Department of Neurology, The Ohio State University College of Medicine, Columbus, OH, USA.
  • Neuroscience Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Institute for Experimental Neuroimmunology, Department of Neurology, Technical University of Munich School of Medicine and Health, Munich, Germany.
  • Munich Cluster for Systems Neurology, Munich, Germany.
  • Center of Neurology, Department of Neuroimmunology and Neuromuscular Diseases, University Hospital and University Bonn, Bonn, Germany.
  • German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • Departments of Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
  • Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, Toulouse, France.
  • Institute for Neuroimmunology and Multiple Sclerosis Research, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.
  • School of Medical Sciences, Neuroscience, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
  • Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Division of Neurosciences, Centre de recherche du CHU de Québec - Université Laval, Quebec City, Quebec, Canada.
  • Department of Molecular Medicine, Université Laval, Quebec City, Quebec, Canada.
  • Mater Research Institute, The University of Queensland, Brisbane, Queensland, Australia.
  • Nash Family Department of Neuroscience, Brain-Body Research Institute, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • School of Biomedical Sciences, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia.
  • Queensland Brain Institute, Faculty of Health, Medicine and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia.
  • Biological Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario, Canada.
  • The Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA.
  • Department of Neurology and Neuroscience, Medical Center, University of Freiburg, Freiburg, Germany.
  • Brain and Mind Centre, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
  • Department of Neurology, Research Center for Immunotherapy (FZI) and Focus Program Translational Neuroscience (FTN), Rhein-Main-Neuronetz (rmn2), University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
  • Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
  • Keenan Research Centre for Biomedical Science at St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada.
  • United Kingdom Dementia Research Institute at the University of Edinburgh, Edinburgh, UK.

Abstract

Neuroimmunology is a rapidly expanding field in which many breakthroughs have been fuelled by studies in animal models that capture aspects of human neurological disease. However, the variety of animal models available, with their relative merits and drawbacks, is not well documented in the literature, posing a hurdle for scientists who are venturing into the world of neuroimmunology. Moreover, nuances between animal models, their utility for studying neuroimmunological processes and the variables that affect their associated clinical and pathological outcomes can affect the reproducibility and clinical relevance of findings at the preclinical stage. In this Review, the International Society of Neuroimmunology White Paper Task Force describes animal models that can be used to study neuroimmunological aspects of neurological disease and the intrinsic and extrinsic factors that affect readouts from these models. We provide guidance on how to manipulate these factors to gain insight into neuroimmunology and to control them for improved reproducibility. We also consider the advantages and limitations of available tools, including robust genetic systems, neuroimmunological imaging, functional readouts and omics-based cell profiling. Finally, we discuss how animal models have advanced drug development to treat neuroimmunological diseases and how the same principles can provide insight into a variety of neurological disorders. We aim to provide guidance on how to optimize the use of animal models to gain insight into neuroimmunological mechanisms and support the preclinical drug discovery pipeline.

MeSH

Pharmaceutical Preparations, Nervous System Diseases