Human CD206+ macrophages associate with diabetes and adipose tissue lymphoid clusters.
Human CD206+ macrophages associate with diabetes and adipose tissue lymphoid clusters.
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DOI：
10.1172/jci.insight.146563
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发表时间：
2022-02-08
期刊：
影响因子：
8
通讯作者：
Lumeng CN
中科院分区：
文献类型：
--
作者：
Muir LA;Cho KW;Geletka LM;Baker NA;Flesher CG;Ehlers AP;Kaciroti N;Lindsly S;Ronquist S;Rajapakse I;O'Rourke RW;Lumeng CN
脂肪组织巨噬细胞（ATM）的增加与人类的代谢功能障碍相关，并且是小鼠胰岛素抵抗发展的原因。最近的批量和单细胞转录组学研究揭示了依赖于上下文的巨噬细胞可能存在的广泛的基因表达特征，但人类ATM亚型的特征在肥胖症和糖尿病中没有很好的定义。我们分析了3种来自肥胖人群脂肪组织的ATM亚型，并确定了它们与2型糖尿病的关系。内脏脂肪组织（VAT）和皮下注射从糖尿病和非糖尿病肥胖参与者中收集脂肪组织（SAT）样品以评价细胞含量和基因表达。VAT CD 206 + CD 11 c − ATM在糖尿病参与者中增加，富含清道夫受体，细胞内脂质低，分泌促炎细胞因子，与2种CD 11 c + ATM亚型显著不同，后者载脂，脂质抗原呈递，与单核细胞特征重叠。此外，糖尿病VAT富含CD 206 + CD 11 c − ATM和炎症特征、清道夫受体和MHC II抗原呈递基因。VAT免疫组化显示，CD 206 + CD 11 c-ATM集中分布于与CD 206-CD 11 c + ATM相邻的血管化淋巴簇中，而CD 206 + CD 11 c+则分布于脂肪细胞之间。我们的研究结果表明，ATM亚型特异性的配置文件，独特的肥胖表型变异的贡献。
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.