Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
Immunology. 2014 Jul;142(3):337-46. doi: 10.1111/imm.12269.
Adipose tissue is a dynamic organ that makes up a substantial proportion of the body; in severe obesity it can account for 50% of body mass. Details of the unique immune system resident in human and murine adipose tissue are only recently emerging, and so it has remained a largely unexplored and unappreciated immune site until now. Adipose tissue harbours a unique collection of immune cells, which often display unusual functions compared with their counterparts elsewhere in the body. These resident immune cells are key to maintaining tissue and immune homeostasis, yet in obesity their chronic aberrant stimulation can contribute to the inflammation and pathogenesis associated with obesity. Anti-inflammatory adipose-resident lymphocytes are often depleted in obesity, whereas pro-inflammatory immune cells accumulate, leading to an overall inflammatory state, which is a key step in the development of obesity-induced metabolic disease. A good example is invariant natural killer T (iNKT) cells, which make up a large proportion of lymphocytes in human and murine adipose tissue. Here, they are unusually poised to produce anti-inflammatory or regulatory cytokines, however in obesity, iNKT cells are greatly reduced. As iNKT cells are potent transactivaors of other immune cells, and can act as a bridge between innate and adaptive immunity, their loss in obesity represents the loss of a major regulatory population. Restoring iNKT cells, or activating them in obese mice leads to improved glucose handling, insulin sensitivity, and even weight loss, and hence represents an exciting therapeutic avenue to be explored for restoring homeostasis in obese adipose tissue.
脂肪组织是一个动态的器官，占人体的很大比例；在严重肥胖的情况下，它可以占到体重的 50%。人类和鼠类脂肪组织中独特的固有免疫系统的细节最近才刚刚出现，因此直到现在，它仍然是一个很大程度上未被探索和未被重视的免疫部位。脂肪组织中存在着独特的免疫细胞群体，与身体其他部位的免疫细胞相比，这些细胞的功能通常不同。这些驻留免疫细胞是维持组织和免疫平衡的关键，但在肥胖症中，它们的慢性异常刺激会导致与肥胖相关的炎症和发病机制。抗炎性脂肪组织驻留淋巴细胞在肥胖症中通常会耗竭，而促炎性免疫细胞则会积累，导致整体炎症状态，这是肥胖引起的代谢性疾病发展的关键步骤。一个很好的例子是不变自然杀伤 T（iNKT）细胞，它们在人类和鼠类脂肪组织中的淋巴细胞中占很大比例。在这里，它们异常地产生抗炎或调节性细胞因子，然而在肥胖症中，iNKT 细胞大大减少。由于 iNKT 细胞是其他免疫细胞的有效转录激活物，并且可以作为先天免疫和适应性免疫之间的桥梁，因此它们在肥胖症中的缺失代表了主要调节群体的缺失。在肥胖小鼠中恢复 iNKT 细胞或激活它们可导致葡萄糖处理、胰岛素敏感性甚至体重减轻得到改善，因此代表了探索恢复肥胖脂肪组织内稳态的令人兴奋的治疗途径。
