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. Animal models are useful tools for studying neuroimmunological aspects of human CNS disease and for identifying therapeutic targets and strategies.
Intrinsic and extrinsic variables can affect the reproducibility and clinical relevance of findings generated from animal models of neuroimmunology. Manipulating intrinsic and extrinsic variables can provide insight into biological influences on neuroimmunological processes; controlling for variables avoids artefacts and confounders to ensure accurate biological interpretations. Continued evolution of scientific tools and approaches will further refine and increase the power of animal models to uncover neuroimmunological processes that are relevant to CNS health.
This is a preview of subscription content, access via your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription Receive 12 print issues and online access Prices may be subject to local taxes which are calculated during checkout Kim, B. The sensory neuroimmune frontier. Immunity 58, 1033–1039 https://doi.org/10.1016/j.immuni.2025.03.018 (2025).
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