10 Chapter 1 IL-10, exhibiting potent anti-inflammatory effects. These macrophages are also characterized by TGFβ production (21). Adipose tissue macrophages Obesity is associated with the development of type 2 diabetes (T2DM), and the immune system in adipose tissue plays a role in this process. Adipose tissue consists of white adipose tissue (WAT) and brown adipose tissue (BAT) (22). In obesity, WAT shows increased levels of pro-inflammatory cytokines, primarily secreted by macrophages (9). Adipose tissue macrophages (ATMs) significantly impact adipose tissue homeostasis. In lean individuals, ATMs resemble M2 macrophages, promoting insulin sensitivity through the production of anti-inflammatory cytokines (23). However, in obesity, excessive growth of WAT leads to lipid accumulation, cellular stress, and hypoxia (24,25), triggering the release of free fatty acids, proinflammatory cytokines, and reactive oxygen species (ROS) (26,27), resulting in impaired insulin sensitivity (28). Monocytes are recruited to adipose tissue in obesity, differentiating into M1-like macrophages that secrete inflammatory factors (29,30). Interestingly, macrophages in obesity display unique characteristics and do not align with the classical activation phenotype (31). They accumulate lipids, express fatty acid transporters such as CD36, and exhibit markers associated with metabolic activation (31,32). These changes in macrophage activation contribute to obesity-related meta-inflammation, characterized by elevated pro-inflammatory cytokines and insulin resistance. The dysregulation of the adipose tissue immune system and the accumulation of inflammatory macrophages play crucial roles in the development and progression of metabolic disorders. Lung macrophages The phenotype and transcriptional signature of alveolar macrophages (AMs), which are macrophages specific to the lung tissue, are shaped by the surrounding lung microenvironment (33). They reside within the alveolar niche, which is composed of type I and type II alveolar epithelial cells, capillary endothelial cells, and alveolar interstitial fibroblasts. This niche provides a cytokine-rich environment that supports the survival and function of AMs (34). In terms of abundance, the lung contains a significant number of AMs. For instance, the upper lobe of the human lung alone houses approximately 1.5 × 109 AMs. The majority of these macrophages are located in the diffusing area of the lung, where they are in close proximity to the gas-exchange region, while a smaller population is found in the conducting small airways (35). Traditionally, AMs were thought to be
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