Modulation of Immune Responses by Metabolic Reprogramming: The Key Role of Immunometabolism

초록

Metabolic regulation is one of the key factors in the direct or indirect control of immune responses. The term “immunometabolism” refers to the study of how metabolic pathways regulate immune responses. This field has gained significant attention over the past few decades, particularly with advances in systems biology, metabolomics, and immunology (1). In addition to the direct regulation of immune cells by metabolic pathways, immune cell- or immune factor-mediated metabolic regulation during inflammatory responses has also emerged as a key area of study. Historically, early research on immunometabolism focused on how energy metabolism supports immune responses. The observation of high glycolytic activity in cancer cells led to the application of similar concepts to immune cell metabolism during immune responses. By the mid-20th century, researchers recognized that immune cell activation was associated with metabolic changes. Studies highlighted that activated T cells rely on aerobic glycolysis, similar to cancer cells, to support rapid proliferation (2). Furthermore, the discovery of mTOR as a key regulator of immune cell metabolism and function provided a mechanistic link between nutrient sensing and immunity (3). Beyond immune cell activation, immunometabolism also plays a critical role in immune cell differentiation and polarization. For instance, inflammatory (M1) macrophages primarily depend on glycolysis, while anti-inflammatory (M2) macrophages rely on oxidative metabolism (4). Additionally, under specific inflammatory conditions, such as within the tumor microenvironment, metabolic changes contribute to immune evasion, significantly influencing cancer immunotherapy (5). Similarly, in infectious diseases, metabolic alterations play a crucial role in immune responses. For example, metabolic dysregulation in immune responses to SARS-CoV-2 has been identified as a major factor in disease progression (6). In this special issue of Immune Network, a collection of review articles provides a comprehensive overview of metabolic regulation in immune cell function and immune cell-mediated disease control. The reviews explore the regulation of various immune cells, including adaptive immune cells, innate lymphoid cells (ILCs), and innate immune cells, through metabolic pathways. Additionally, they address specific immune-related conditions such as the tumor microenvironment, host-microbiota interactions, aging, and metabolic diseases.

키워드