Intestinal challenges shape the polarisation of protective dural memory CD4 T cells Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.1101/2025.09.09.673536
· OA: W4414258690
The meninges house several innate and adaptive immune cell populations 1–3 . These predominantly localise within the dura mater and include gut-derived IgA-secreting plasma cells 4 . Whether T cell adaptive memory in the dura is similarly linked to the gut is currently unknown. Here we show that dural CD4 T cell polarisation to a T helper (Th) 1, Th2 and Th17 state is determined by the nature of the immunological challenge encountered in the gastrointestinal tract. We find that intestinally polarised CD4 T cells seed to the dura in a CXCR6-CXCL16-dependent manner, express tissue-residency markers and are long-lived. Functionally, these orally-primed dural CD4 T are capable of a rapid antigen-specific recall response that limits pathogen spread into the brain following intravenous re-challenge. Our work reveals how linked intestinal and dural immunity enables the central nervous system to accrue immunological memory of gut microbes, the most likely source of life-threatening bloodborne pathogens.
