Obesity is understood to be an inflammatory condition characterized in part by changes in resident immune cell populations in adipose tissue. However, much of this knowledge has been obtained through experimental animal models. Epigenetic mechanisms, such as DNA methylation may be useful tools for characterizing the changes in immune cell populations in human subjects. In this study, we introduce a simple and intuitive method for assessing cellular infiltration by blood into other heterogeneous, admixed tissues such as adipose tissue, and apply this approach in a large human cohort study. Associations between higher leukocyte infiltration, measured by evaluating a distance measure between the methylation signatures of leukocytes and adipose tissue, and increasing body mass index (BMI) or android fat mass (AFM) were identified and validated in independent replication samples for CD4 (pBMI  = 0.009, pAFM  = 0.020), monocytes (pBMI  = 0.001, pAFM  = 4.3 × 10-4 ), and dendritic cells (pBMI  = 0.571, pAFM  = 0.012). Patterns of depletion with increasing adiposity were observed for plasma B (pBMI  = 0.430, pAFM  = 0.004) and immature B (pBMI  = 0.022, pAFM  = 0.042) cells. CD4, dendritic, monocytes, immature B, and plasma B cells may be important agents in the inflammatory process. Finally, the method used to assess leukocyte infiltration in this study is straightforwardly extended to other cell types and tissues in which infiltration might be of interest.

中文翻译：

---

利用细胞特异性差异甲基化区域来识别脂肪组织中的白细胞浸润。

肥胖被认为是一种炎症性疾病，其部分特征是脂肪组织中常驻免疫细胞群的变化。然而，大部分知识是通过实验动物模型获得的。DNA甲基化等表观遗传机制可能是表征人类受试者免疫细胞群变化的有用工具。在这项研究中，我们介绍了一种简单直观的方法来评估血液对其他异质混合组织（如脂肪组织）的细胞浸润，并将这种方法应用于大型人类队列研究。通过评估白细胞和脂肪组织甲基化特征之间的距离测量来测量较高的白细胞浸润与体重指数 (BMI) 或机器人脂肪量 (AFM) 的增加之间的关联，并在 CD4 的独立复制样本中进行了鉴定和验证 (pBMI = 0.009，pAFM = 0.020），单核细胞（pBMI = 0.001，pAFM = 4.3 × 10-4）和树突状细胞（pBMI = 0.571，pAFM = 0.012）。观察到血浆 B (pBMI = 0.430, pAFM = 0.004) 和未成熟 B (pBMI = 0.022, pAFM = 0.042) 细胞随着肥胖程度增加而消耗的模式。CD4、树突状细胞、单核细胞、未成熟 B 细胞和血浆 B 细胞可能是炎症过程中的重要因子。最后，本研究中用于评估白细胞浸润的方法可以直接扩展到可能对浸润感兴趣的其他细胞类型和组织。