Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance.
Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance.
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DOI：
10.4049/jimmunol.1600820
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发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Lumeng CN
中科院分区：
文献类型：
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作者：
Cho KW;Zamarron BF;Muir LA;Singer K;Porsche CE;DelProposto JB;Geletka L;Meyer KA;O'Rourke RW;Lumeng CN
脂肪组织白细胞，包括脂肪组织巨噬细胞（ATM）和脂肪组织树突状细胞（ATDC）的动态变化有助于肥胖诱导的炎症和代谢疾病。然而，脂肪组织中ATDC和ATM的明确区分限制了免疫代谢领域的进展。在这项研究中，我们利用CD64来区分ATM和ATDC，并研究了肥胖期间这些髓系人群的时间和功能变化。流式细胞术和免疫染色表明，ATM的定义为F4/80+CD11b+细胞与其他白细胞重叠，CD45+CD64+是ATM特异性的。核心DC基因在CD11c+CD64−细胞（ATDC）中表达富集，而核心巨噬细胞基因在CD45+CD64+细胞（ATM）中表达富集。CD11c+CD64−ATDC表达MHCII和共刺激受体，具有与ATM相似的刺激CD4+ T细胞增殖的能力。ATDC主要是CD11b+常规dc，并且在中等高脂饮食暴露的脂肪组织中占CD11c+细胞的大部分。与Ccr2 - / -小鼠的混合嵌合实验表明，高脂肪饮食（HFD）诱导单核细胞的ATM积累依赖于Ccr2；而ATDC积累较少依赖ccr2。肥胖期间ATDC的积累在Ccr7−/−小鼠中减弱，并与脂肪组织炎症和胰岛素抵抗的减少有关。在人类肥胖脂肪组织中发现了CD45+CD64+ ATM和CD45+CD64−CD11c+ ATDC，与网膜相比，皮下脂肪组织中的ATDC增加。这些结果支持了明确描述ATM和ATDC的修订策略，并表明ATDC是肥胖期间脂肪组织炎症的独立贡献者。
Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDC) contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we utilize CD64 to distinguish ATM and ATDC and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80+CD11b+ cells overlaps with other leukocytes and that CD45+CD64+ is specific for ATM. The expression of core DC genes were enriched in CD11c+CD64− cells (ATDC), while core macrophage genes were enriched in CD45+CD64+ cells (ATM). CD11c+CD64− ATDC expressed MHCII and co-stimulatory receptors and had similar capacity to stimulate CD4+ T cell proliferation as ATM. ATDC were predominantly CD11b+ conventional DCs and made up the bulk of CD11c+ cells in adipose tissue with moderate high fat diet exposure. Mixed chimeric experiments with Ccr2−/− mice demonstrated that high-fat diet (HFD) induced ATM accumulation from monocytes was dependent on CCR2; while ATDC accumulation was less CCR2-dependent. ATDC accumulation during obesity was attenuated in Ccr7−/− mice and was associated with decreased adipose tissue inflammation and insulin resistance. CD45+CD64+ ATM and CD45+CD64−CD11c+ ATDC were identified in human obese adipose tissue and ATDC were increased in subcutaneous adipose tissue compared to omental. These results support a revised strategy for unambiguous delineation of ATM and ATDC and suggests that ATDC are independent contributors to adipose tissue inflammation during obesity.
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影响因子：
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作者：
Cho, Kae Won;Morris, David L.;Lumeng, Carey N.
通讯作者：
Lumeng, Carey N.
影响因子：
5.4
作者：
De Calisto, Jaime;Villablanca, Eduardo J.;Mora, J. Rodrigo
通讯作者：
Mora, J. Rodrigo
影响因子：
7.7
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
通讯作者：
Saltiel, Alan R.
影响因子：
6.4
作者：
Collin M;McGovern N;Haniffa M
通讯作者：
Haniffa M
影响因子：
30.5
作者：
通讯作者：
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