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Remote hyperinflammation drives neurological disease via T-cell-mediated innate-like cytotoxicity

Cellular & Molecular Immunology volume 18, pages 1638–1640 (2021)Cite this article

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Inflammation is critical for the induction of immune responses to pathogens and other foreign substances. However, excessive local and systemic inflammation can have dire consequences beyond the original site of inflammation. A link between peripheral inflammation and neuropathology has been suggested for many diseases, including influenza infection, liver cirrhosis, and irritable bowel syndrome.1,2,3 Arguably, the vast majority of inflammatory diseases have been associated with deleterious neurological outcomes. Likewise, immunotherapies, such as CAR T-cell treatment, are known for their high risk of cytokine release syndrome and associated neurotoxicity. However, the mechanism behind this phenomenon of inflammation-induced neuropathology remains largely misunderstood. Preclinical evidence from animal models that accurately depict this phenomenon is limited; these models will be essential to uncover the role of peripheral inflammation in neurological complications of disease. Beginning to fill this gap in understanding, Zhou et al. reported critical evidence linking lymphocytes from the inflamed gut to neurological sequelae in infants with necrotizing enterocolitis (NEC).4 These results pave the way to understanding how peripheral inflammation can adversely enhance immune activation and result in downstream neurological disease.

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Fig. 1: Mechanisms of hyperinflammation-induced T cell activation and innate-like cytotoxicity.

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Acknowledgements

Elizabeth Balint is a recipient of the Frederick Banting and Charles Best Canada Graduate Scholarship-Master’s from the Canadian Institutes of Health Research. Ali Ashkar is also a recipient of a CIHR Tier 1 Canada Research Chair.

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  1. Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada

    Elizabeth Balint & Ali A. Ashkar

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  1. Elizabeth Balint
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Correspondence to Ali A. Ashkar.

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Balint, E., Ashkar, A.A. Remote hyperinflammation drives neurological disease via T-cell-mediated innate-like cytotoxicity. Cell Mol Immunol 18, 1638–1640 (2021). https://doi.org/10.1038/s41423-021-00705-9

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