T-cell distribution in the dorsal root ganglion across species, sex, and age
T-cells infiltrate somatosensory ganglia in response to nerve damage, autoimmune disease, and infection, contributing to sensory abnormalities and pain. In naive states, T-cells are rare in the rodent dorsal root ganglion (DRG) but have been reported in human and non-human primates without known relevant exposures. It remains unclear whether there are inherent evolutionary or species differences in DRG T-cell residence. Using a comparative biology approach, we investigated the frequency and distribution of T-cells in the mammalian DRG across humans, non-human primates, pigs, and rodents, and in humans investigated the contributions of sex and age. Spatial transcriptomics and immunofluorescence independently verified the robust presence of DRG T-cells at similar levels in humans, non-human primates, and pigs, but were fewer in rats and largely absent in mice. In humans, premenopausal females were more likely to have elevated DRG endoneurial T-cells than post-menopausal females or adult males. T-cells were detected in human dorsal root ganglion at as early as two months of age but were less abundant within the perineuronal niche. Most human DRG T-cells expressed distinct markers consistent with a resident memory (Trm) phenotype. We discuss the importance of studying the functional roles of DRG-resident T-cells and raise broader considerations for modelling peripheral nervous system disease. ### Competing Interest Statement TJP is co-founder of 4E Therapeutics, PARMedics, NuvoNuro, Nerveli, and Ted and Gregs. National Institutes of Health, https://ror.org/01cwqze88, U19NS130608
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