Chronic peripheral inflammation causes a region-specific myeloid response in the central nervous system

Systemic immune dysregulation contributes to the development of neuropsychiatric and neurodegenerative diseases. The precise effect of chronic peripheral immune stimulation on myeloid cells across anatomical brain regions is unclear. We used the human TNF-α transgenic mouse model of RA (TNFtg mice, strain Tg197) (Keffer et al., 1991), which shows increased levels of peripheral cytokines and severe joint pathology at young age and leads to severe disability within 3-4 months after birth (Keffer et al., 1991; Suss et al., 2015) to assess the effect of chronic peripheral inflammation on myeloid cells in the cortex. To examine the response of brain myeloid cells to systemic chronic inflammation, we performed single cell RNA-seq on isolated CD11b+CD45+ cells from the cortex of wt and TNFtg mice. Single cell RNA-seq of cortical myeloid (CD45+) cells from C57Bl6/J wild type and TNF transgenic mice