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脂肪组织中免疫抑制细胞的频率在人类、非人类灵长类动物和小鼠模型中存在差异。

The Frequencies of Immunosuppressive Cells in Adipose Tissue Differ in Human, Non-human Primate, and Mouse Models.

机构信息

CEA - Université Paris Sud 11 - INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Fontenay-aux-Roses, France.

Assistance Publique Hôpitaux de Paris, Hôpital Bicêtre, Service de Chirurgie Digestive et Oncologique, Le Kremlin-Bicêtre, France.

出版信息

Front Immunol. 2019 Feb 5;10:117. doi: 10.3389/fimmu.2019.00117. eCollection 2019.

Abstract

Although the metabolic properties of white adipose tissue have been extensively characterized, the tissue's immune properties are now attracting renewed interest. Early experiments in a mouse model suggested that white adipose tissue contains a high density of regulatory T cells (Tregs), and so it was assumed that all adipose tissue has an immunosuppressive profile-even though the investigation was limited to visceral body fat in relatively old male mice. This observation was also corroborated by high frequencies of other cell subsets with immunoregulatory properties, such as anti-inflammatory M2 macrophages, and regulatory B cells. Many studies have since evidenced the persistence of pathogens (trypanosomes, , HIV, etc.) in adipose tissue. However, a recent report identified adipose tissue as a reservoir of memory T cells capable of protecting animals upon rechallenge. The immune potential of lean adipose tissue thus remains to be further investigated. Here, we compared the relative proportions of immune cells (and Tregs in particular) in lean adipose tissue collected from humans, a non-human primate (the cynomolgus macaque), and three mouse models. We demonstrated that the proportion of Foxp3+ Tregs in visceral adipose tissue was low in all models other than the C57Bl/6 mouse. These low values were not linked to correspondingly low proportions of effector cells because T lymphocytes (a main target of Treg suppression) were more frequent in cynomolgus macaques than in C57Bl/6 mice and (to a lesser extent) humans. In contrast, the proportions of macrophages and B cells were lower in cynomolgus macaques than in C57Bl/6 mice. We also observed a higher proportion of CD34+CD45- cells (which predominantly correspond to mesenchymal stem cells) in C57Bl/6 mouse and cynomolgus macaques than in humans and both for subcutaneous and visceral adipose tissues. Lastly, a microscopy analysis confirmed predominant proportion of adipocytes within adipose tissue, and highlighted a marked difference in adipocyte size among the three species studied. In conclusion, our study of lean, middle-aged, male individuals showed that the immune compartment of adipose tissue differed markedly in humans vs. mice, and suggesting the presence of a more inflammatory steady-state profile in humans than mice.

摘要

尽管白色脂肪组织的代谢特性已得到广泛研究,但该组织的免疫特性现在重新引起了人们的兴趣。在小鼠模型的早期实验中,人们发现白色脂肪组织中含有高密度的调节性 T 细胞(Tregs),因此人们认为所有脂肪组织都具有免疫抑制特性——尽管这项研究仅限于相对较老的雄性小鼠的内脏脂肪。这一观察结果也得到了其他具有免疫调节特性的细胞亚群(如抗炎 M2 巨噬细胞和调节性 B 细胞)高频率存在的证实。此后,许多研究证实了病原体(锥虫、HIV 等)在脂肪组织中的持续存在。然而,最近的一份报告指出,脂肪组织是记忆 T 细胞的储存库,这些细胞能够在再次受到攻击时保护动物。因此,瘦脂肪组织的免疫潜力仍有待进一步研究。在这里,我们比较了从人类、非人类灵长类动物(食蟹猴)和三种小鼠模型中收集的瘦脂肪组织中免疫细胞(特别是 Tregs)的相对比例。我们发现,除 C57Bl/6 小鼠外,其他所有模型的内脏脂肪组织中 Foxp3+Tregs 的比例都很低。这些低值与效应细胞的比例相应较低无关,因为 T 淋巴细胞(Treg 抑制的主要靶标)在食蟹猴中比在 C57Bl/6 小鼠中更常见(在较小程度上),并且比人类更常见。相比之下,巨噬细胞和 B 细胞在食蟹猴中的比例低于 C57Bl/6 小鼠。我们还观察到 C57Bl/6 小鼠和食蟹猴的皮下和内脏脂肪组织中 CD34+CD45-细胞(主要对应间充质干细胞)的比例较高。最后,显微镜分析证实了脂肪组织中脂肪细胞的主导比例,并强调了三种研究物种之间脂肪细胞大小的显著差异。总之,我们对中年、雄性瘦个体的研究表明,脂肪组织的免疫成分在人类与小鼠之间存在显著差异,并表明人类的稳态炎症状态比小鼠更为明显。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d1/6371887/ecba7a85f272/fimmu-10-00117-g0001.jpg

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