Pig model uncovers microglia–T cell crosstalk in Huntington’s disease

lab animal Research highlights Neurodegenerative disease https://doi.org/10.1038/s41684-026-01714-9 Pig model uncovers microglia–T cell crosstalk in Huntington’s disease Check for updates In a study published in Nature Biomedical Engineering, researchers used their previously established and genetically engineered pig model of Huntington’s disease (HD) to uncover immune-neural interactions that drive neurodegeneration. HD, caused by an expanded CAG repeat in exon 1 of the HTT gene, leads to progressive motor and cognitive decline and is characterized by atrophy of the striatum and loss of medium spiny neurons in this brain region. Although rodent HD knock-in models partly reproduce molecular pathology, they fail to show the selective neuronal loss seen in patients, limiting their utility for investigating disease mechanisms. Here, the team used single nucleus and spatial transcriptomics integrated with immunohistochemistry to generate a cellular map of the HD pig striatum. They compared the results with control pigs and data from HD mouse models and patients with HD. The comparative analysis revealed that while major striatal cell types were conserved across species, key differences emerged. Notably, while HD pig and human striatal tissues both showed selective neuronal loss and pronounced CD8⁺ T cell infiltration, these features were absent in HD mice. In the striatum of HD pigs, the team also identified an interferon-responsive microglial subset that secretes CCL8, a chemokine that recruits cytotoxic CD8⁺ T cells. These T cells release perforin and granzyme, most likely accelerating neuronal loss in HD pigs. Adenovirus-mediated overexpression of CCL8 in the striatum of HD mice induced CD8+ T cell infiltration and neurodegeneration, mirroring the pig phenotype. Overall, the study reveals a speciesdependent microglia–T cell axis that contributes to striatal degeneration in HD and highlights CCL8-mediated T-cell recruitment as a potential therapeutic target. Alexandra Le Bras Original reference: Li, J. et al. Nat. Biomed. Eng. (2026) https://doi.org/10.1038/s41551-026-01621-x Build your skills. Boost your confidence and advance your scientific research with researcher training from Nature Masterclasses Choose from live workshops, or learn at your own pace with the Nature Masterclasses on-demand platform. Gain insights and learn from Nature Portfolio journal Editors and industry experts. Wherever you are on your research journey, we’re here to help. Access our free courses, plus free course samples and find out more at: masterclasses.nature.com @Nature Masterclasses 03GAS / Image credit: Cavan Images Lab Animal | Volume 55 | April 2026 | 106 106  (...truncated)