State of the union between metabolism and the immune system in type 2 diabetes.
State of the union between metabolism and the immune system in type 2 diabetes.
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DOI：
10.1038/gene.2011.14
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发表时间：
2011-06
影响因子：
5
通讯作者：
Gyurko R
中科院分区：
文献类型：
--
作者：
Nikolajczyk BS;Jagannathan-Bogdan M;Shin H;Gyurko R
淋巴细胞和骨髓细胞（单核细胞/巨噬细胞）在多种以未解决炎症为特征的疾病中发挥重要作用。最近人们将肥胖、胰岛素抵抗和 2 型糖尿病 (T2D) 视为慢性炎症性疾病，这激发了人们对了解免疫细胞在代谢失衡中的作用的兴趣。骨髓细胞通过细胞因子的产生和伴随营养过剩的脂肪组织重塑来调节炎症，因此是代谢稳态的关键参与者。最近，多项研究表明 T 细胞在模型生物体中与肥胖相关的炎症和胰岛素抵抗中发挥作用，同时开展的研究表明 T 细胞的促炎症变化也与人类 T2D 相关。此外，肥胖和 T2D 中具有相似抗原结合位点的 T 细胞的扩增表明这些疾病具有先前归因于炎症性自身免疫性疾病的特征。 T2D 患者 B 细胞区室中的平行促炎变化也已被发现。总而言之，这些研究表明，除了公认的骨髓细胞在 T2D 中的促炎作用之外，两种主要淋巴细胞亚群的促炎偏向在 T2D 疾病发病机制中也具有重要作用。基本免疫学原理表明，肥胖和 T2D 患者淋巴细胞功能的改变是涉及其他细胞类型的前馈促炎循环的一个组成部分。重要的是，促炎循环几乎不可避免地包括脂肪细胞，已知脂肪细胞会对源自骨髓和淋巴室的促炎、促糖尿病细胞因子做出反应。我们提出了一种 T2D 炎症模型，该模型在功能上将淋巴细胞、骨髓细胞和脂肪细胞的贡献联系起来，并且重要的是提出用于 B 细胞消融或 T 细胞亚群平衡调节的工具可能在内分泌学家有限的武器库中占有一席之地。
Lymphocytes and myeloid cells (monocyte/macrophages) have important roles in multiple types of diseases characterized by unresolved inflammation. The relatively recent appreciation of obesity, insulin resistance and type 2 diabetes (T2D) as chronic inflammatory diseases has stimulated interest in understanding the role of immune cells in metabolic imbalance. Myeloid cells regulate inflammation through cytokine production and the adipose tissue remodeling that accompanies hyper-nutrition, thus are critical players in metabolic homeostasis. More recently, multiple studies have indicated a role for T cells in obesity-associated inflammation and insulin resistance in model organisms, with parallel work indicating that pro-inflammatory changes in T cells also associate with human T2D. Furthermore, the expansion of T cells with similar antigen-binding sites in obesity and T2D indicates these diseases share characteristics previously attributed to inflammatory autoimmune disorders. Parallel pro-inflammatory changes in the B-cell compartment of T2D patients have also been identified. Taken together, these studies indicate that in addition to accepted pro-inflammatory roles of myeloid cells in T2D, pro-inflammatory skewing of both major lymphocyte subsets has an important role in T2D disease pathogenesis. Basic immunological principles suggest that alterations in lymphocyte function in obesity and T2D patients are an integral part of a feed-forward pro-inflammatory loop involving additional cell types. Importantly, the pro-inflammatory loop almost inevitably includes adipocytes, known to respond to pro-inflammatory, pro-diabetogenic cytokines originating from the myeloid and lymphoid compartments. We propose a model for inflammation in T2D that functionally links lymphocyte, myeloid and adipocyte contributions, and importantly proposes that tools for B-cell ablation or regulation of T-cell subset balance may have a place in the endocrinologist’s limited arsenal.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
9.3
作者：
Al-Attas OS;Al-Daghri NM;Al-Rubeaan K;da Silva NF;Sabico SL;Kumar S;McTernan PG;Harte AL
通讯作者：
Harte AL
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
158.5
作者：
Edwards, JCW;Szczepanski, L;Shaw, T
通讯作者：
Shaw, T
影响因子：
2.8
作者：
Berchtold, Lukas A.;Larsen, Claus M.;Mandrup-Poulsen, Thomas
通讯作者：
Mandrup-Poulsen, Thomas