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

JCI Insight. 2022 Feb 8;7(3):e146563. doi: 10.1172/jci.insight.146563.


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.

Keywords: Adipose tissue; Diabetes; Immunology; Macrophages; Metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation*
  • Humans
  • Insulin Resistance / genetics*
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / genetics*
  • Time Factors
  • Young Adult


  • MRC1 protein, human
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • DNA