Human CD206(+) macrophages associate with diabetes and adipose tissue clustersopen access
- Authors
- Muir, Lindsey A.; Cho, Kae Won; Geletka, Lynn M.; Baker, Nicki A.; Flesher, Carmen G.; Ehlers, Anne P.; Kaciroti, Niko; Lindsly, Stephen; Ronquist, Scott; Rajapakse, Indika; O'Rourke, Robert W.; Lumeng, Carey N.
- Issue Date
- 8-Feb-2022
- Publisher
- The American Society for Clinical Investigation
- Citation
- JCI insight, v.7, no.3, pp 1 - 17
- Pages
- 17
- Journal Title
- JCI insight
- Volume
- 7
- Number
- 3
- Start Page
- 1
- End Page
- 17
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/20546
- DOI
- 10.1172/jci.insight.146563
- ISSN
- 2324-7703
2379-3708
- Abstract
- Increased adipose tissue macrophages (ATMs) correlate with metabolic dysfunction in humans and are causal in development of insulin resistance in mice. Recent bulk and single-cell transcriptomics studies reveal a wide spectrum of gene expression signatures possible for macrophages that depends on context, but the signatures of human ATM subtypes are not well defined in obesity and diabetes. We profiled 3 prominent ATM subtypes from human adipose tissue in obesity and determined their relationship to type 2 diabetes. Visceral adipose tissue (VAT) and s.c. adipose tissue (SAT) samples were collected from diabetic and nondiabetic obese participants to evaluate cellular content and gene expression. VAT CD206(+)CD11c(-) ATMs were increased in diabetic participants, were scavenger receptor-rich with low intracellular lipids, secreted proinflammatory cytokines, and diverged significantly from 2 CD11c(+) ATM subtypes, which were lipid-laden, were lipid antigen presenting, and overlapped with monocyte signatures. Furthermore, diabetic VAT was enriched for CD206(+)CD11c(-) ATM and inflammatory signatures, scavenger receptors, and MHC II antigen presentation genes. VAT immunostaining found CD206(+)CD11c(-) ATMs concentrated in vascularized lymphoid clusters adjacent to CD206(-)CD11c(+) ATMs, while CD206(+)CD11c+ were distributed between adipocytes. Our results show ATM subtype-specific profiles that uniquely contribute to the phenotypic variation in obesity.
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Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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