| Title: |
Single-cell transcriptome profiling reveals heterogeneity of brain myeloid cells and unique subsets that regulate T cell immunity and cerebrovascular inflammation in diet-induced obesity |
| Authors: |
Yu, I-Chen Ivorine; Paraiso, Hallel C; Kuo, Ping-Chang; Furnas, Destin J; Scofield, Barbara A; Weng, Wen-Tsan; Sweazey, Robert D; Chang, Fen-Lei; Yen, Jui-Hung |
| Source: |
The Journal of Immunology ; volume 204, issue 1_Supplement, page 69.4-69.4 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2020 |
| Description: |
Midlife obesity and type 2 diabetes mellitus (T2DM) are linked to decreased cognition and strong risk for Alzheimer’s disease in late life. Previous studies show that obesity/T2DM is associated with a heightened state of neuroinflammation in aging mice. However, it remains unclear how diverse immune cell populations in the brain contribute to the cognitive decline. To address this, we fed middle-aged mice with high-fat diet (HFD) to induce visceral obesity and hyperglycemia. Chronic HFD consumption resulted in cognitive impairment and activation of brain resident microglia (MG). The CD45hiCD11b+ peripheral myeloid cells and CD3+ T cells were significantly increased in the brain of obese mice. Single-cell RNA sequencing was performed to characterize CD11b+ cells isolated from the brain. Unsupervised clustering singled out distinct myeloid cell clusters. Using Tmem119 and P2ry12 as markers to distinguish MG from infiltrating cells, we observed a 2-fold increase of peripheral myeloid cells, comprising distinct clusters in HFD-fed mice. Multiple subsets of MG were identified in HFD-fed mice, showing Ms4a, Apoe and gene signatures of perivascular macrophages. Notably, these subsets expressed high levels of MHC class-II-related molecules, H2-Eb1, H2-Ab1, and Cd74, and with special functions in lipid metabolism. These data suggested possible interactions between MG and T cells to potentiate neuroinflammation in HFD-fed mice. Overall, our results highlighted heterogeneity of brain myeloid cells in obesity during aging. The identified subsets of MG provide insights into brain MG controlling T cell immunity and cerebrovascular inflammation, which might lead to cognitive impairment associated with obesity and T2DM during aging. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.204.supp.69.4 |
| Availability: |
https://doi.org/10.4049/jimmunol.204.supp.69.4; https://academic.oup.com/jimmunol/article/204/1_Supplement/69.4/7948630 |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.F6EB3F97 |
| Database: |
BASE |