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Human CD206+ macrophages associate with diabetes and adipose tissue lymphoid clusters
Lindsey A. Muir, … , Robert W. O’Rourke, Carey N. Lumeng
Lindsey A. Muir, … , Robert W. O’Rourke, Carey N. Lumeng
Published January 6, 2022
Citation Information: JCI Insight. 2022;7(3):e146563. https://doi.org/10.1172/jci.insight.146563.
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Research Article Immunology Metabolism Article has an altmetric score of 7

Human CD206+ macrophages associate with diabetes and adipose tissue lymphoid clusters

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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.

Authors

Lindsey A. Muir, Kae Won Cho, Lynn M. Geletka, Nicki A. Baker, Carmen G. Flesher, Anne P. Ehlers, Niko Kaciroti, Stephen Lindsly, Scott Ronquist, Indika Rajapakse, Robert W. O’Rourke, Carey N. Lumeng

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Figure 3

CD206+ ATMs are distinct from other subtypes.

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CD206+ ATMs are distinct from other subtypes.
(A) Dendrogram based on th...
(A) Dendrogram based on the top 500 variably expressed genes (left) and PCA (right) of human ATM subtypes. The 3 ATM subtypes were each isolated from 3 patient samples with obesity (2 DM, 1 NDM) for a total of 9 analyzed cell populations. (B) Distance diagram between ATM subtypes based on DE genes for each comparison. (C) Top pathways distinguishing ATM subtypes. (D) Scavenger receptor–related gene expression in ATM subtypes. (E) Overlap of ATM subtypes with Vijay et al. data (13). Fold difference in expression for each comparison is shown, with gray bars showing expression in CD206+ ATMs, dark blue in CD11c+ ATMs, and light blue in DP ATMs. Overlap was defined as a higher percentage of mutual genes than the overall mean percentage of mutual genes across all 5 Vijay populations. (F) Overlap of ATM subtypes with Wentworth et al. data (9). (G) Overlap of ATM subtypes with monocytes in obesity (GSE32575). (H) MacSpectrum analysis of ATM subtypes. MPI, macrophage polarization index; AMDI, activation induced differentiation index.

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