Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences
Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences
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DOI：
10.4049/jimmunol.175.1.342
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Suttles, J
中科院分区：
文献类型：
--
作者：
Stout, RD;Jiang, CC;Suttles, J
最近的研究描述了巨噬细胞不同功能亚群的发展与癌症、自身免疫性疾病和慢性感染有关。基于Th1和Th2细胞因子在巨噬细胞中促进对立活动的能力，有人提出巨噬细胞可发展为1型炎症亚群或2型抗炎亚群。作为亚群发育概念的另一种选择，我们提出巨噬细胞作为对其组织环境变化的反应，可以可逆地逐步改变其表达的功能模式。如本文所示，巨噬细胞可以通过多种模式可逆地改变其功能表型，以响应细胞因子环境的变化。巨噬细胞在ifn - γ、IL-12、IL-4或IL-10治疗后显示出不同的功能模式，其他功能模式的显示取决于细胞因子是单独存在还是与其他细胞因子一起存在，以及细胞因子是在激活刺激（LPS）之前添加还是伴随添加。用多种细胞因子序贯治疗巨噬细胞可导致多种功能表型的进展。这种适应不断变化的细胞因子环境的能力在体内具有重要的相关性，正如在老年或荷瘤小鼠体内建立的巨噬细胞功能表型可以通过改变其微环境来改变的证明。本文提出了一个功能适应性的概念，它对慢性疾病中巨噬细胞的治疗靶向具有重要意义，导致巨噬细胞的特定功能表型在疾病病理中发挥重要作用。
Recent studies have described the development of distinct functional subsets of macrophages in association with cancer, autoimmune disease, and chronic infections. Based on the ability of Th1 vs Th2 cytokines to promote opposing activities in macrophages, it has been proposed that macrophages develop into either type 1 inflammatory or type 2 anti-inflammatory subsets. As an alternative to the concept of subset development, we propose that macrophages, in response to changes in their tissue environment, can reversibly and progressively change the pattern of functions that they express. As demonstrated herein, macrophages can reversibly shift their functional phenotype through a multitude of patterns in response to changes in cytokine environment. Macrophages display distinct functional patterns after treatment with IFN-gamma, IL-12, IL-4, or IL-10 and additional functional patterns are displayed depending on whether the cytokine is present alone or with other cytokines and whether the cytokines are added before or concomitantly with the activating stimulus (LPS). Sequential treatment of macrophages with multiple cytokines results in a progression through multiple functional phenotypes. This ability to adapt to changing cytokine environments has significant in vivo relevance, as evidenced by the demonstration that macrophage functional phenotypes established in vivo in aged or tumor-bearing mice can be altered by changing their microenvironment. A concept of functional adaptivity is proposed that has important implications for therapeutic targeting of macrophages in chronic diseases that result in the dominance of particular functional phenotypes of macrophages that play a significant role in disease pathology.