The brain and its borders create a highly dynamic microenvironment populated with immune cells. Yet characterization of immune cells within the naive brain compartment remains limited. In this study, we used CyTOF mass cytometry to characterize the immune populations of the naive mouse brain using 44 cell surface markers. By comparing immune cell composition and cell profiles between the brain compartment and blood, we were able to characterize previously undescribed cell subsets of CD8 T cells, B cells, NK cells and dendritic cells in the naive brain. Using flow cytometry, we show differential distributions of immune populations between meninges, choroid plexus and parenchyma. We demonstrate the phenotypic ranges of resident myeloid cells and identify CD44 as a marker for infiltrating immune populations. This study provides an approach for a system-wide view of immune populations in the brain and is expected to serve as a resource for understanding brain immunity.
Regulating immunity is a leading target for cancer therapy. Here, we show that the anti-tumor immune response can be modulated by the brain’s reward system, a key circuitry in emotional processes. Activation of the reward system in tumor-bearing mice (Lewis lung carcinoma (LLC) and B16 melanoma) using chemogenetics (DREADDs), resulted in reduced tumor weight. This effect was mediated via the sympathetic nervous system (SNS), manifested by an attenuated noradrenergic input to a major immunological site, the bone marrow. Myeloid derived suppressor cells (MDSCs), which develop in the bone marrow, became less immunosuppressive following reward system activation. By depleting or adoptively transferring the MDSCs, we demonstrated that these cells are both necessary and sufficient to mediate reward system effects on tumor growth. Given the central role of the reward system in positive emotions, these findings introduce a physiological mechanism whereby the patient’s psychological state can impact anti-tumor immunity and cancer progression.
In the originally published version of this article, we reported that neurons in the insular cortex encode and retrieve specific immune responses. We have identified minor errors in the STAR Methods section, which are located in the paragraph entitled ''Activitydependent cell labeling.'' First, the amount of Tamoxifen injected into the mice should be 150 mg/kg instead of 15 mg/kg as we originally stated. Second, the injected dose of the 4-OHT final solution is missing from the text; it should be 50 mg/kg. We have also corrected errors in the reporting of the n values for experiments in the figure legends (Figures 2C, 2D, 2P, 3F, and 3H) and the y-axis description for Figure S5M.
Highlights d Optogenetic activation of local sympathetic fibers in the colon attenuates colitis d The local sympathetic activation reduces immune cell abundance d Reduction in immune abundance is mediated by a decrease in endothelial MAdCAM-1
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