Immuno-Biology Lab, Translational Health Science and Technology Institute, Faridabad, India.
Front Immunol. 2019 Jan 14;9:3036. doi: 10.3389/fimmu.2018.03036. eCollection 2018.
Naïve CD4 T cell differentiate into effector and regulatory subsets of helper T (Th) cells in various pathophysiological conditions and modulate tissue inflammation in autoimmune diseases. While cytokines play a key role in determining the fate of Th cells differentiation, metabolites, and metabolic pathways profoundly influence Th cells fate and their functions. Emerging literature suggests that interplay between metabolic pathways and cytokines potentiates T cell differentiation and functions in tissue inflammation in autoimmune diseases. Metabolic pathways, which are essential for the differentiation and functions of Th cell subsets, are regulated by cytokines, nutrients, growth factors, local oxygen levels, co-activation receptors, and metabolites. Dysregulation of metabolic pathways not only alters metabolic regulators in Th cells but also affect the outcome of tissue inflammation in autoimmune and allergic diseases. Understanding the modulation of metabolic pathways during T cells differentiation may potentially lead to a therapeutic strategy for immune-modulation of autoimmune and allergic diseases. In this review, we summarize the role of metabolic checkpoints and their crosstalk with different master transcription factors and signaling molecules in differentiation and function of Th subsets, which may potentially unravel novel therapeutic interventions for tissue inflammation and autoimmune disorders.
幼稚 CD4 T 细胞在各种病理生理条件下分化为辅助性 T（Th）细胞的效应和调节亚群，并调节自身免疫性疾病中的组织炎症。虽然细胞因子在决定 Th 细胞分化命运方面发挥着关键作用，但代谢物和代谢途径也深刻影响 Th 细胞的命运及其功能。新出现的文献表明，代谢途径和细胞因子之间的相互作用增强了自身免疫性疾病中组织炎症中的 T 细胞分化和功能。代谢途径对于 Th 细胞亚群的分化和功能至关重要，其受到细胞因子、营养物质、生长因子、局部氧水平、共激活受体和代谢物的调节。代谢途径的失调不仅改变了 Th 细胞中的代谢调节剂，还影响了自身免疫和过敏疾病中组织炎症的结果。了解 T 细胞分化过程中的代谢途径调节可能为免疫调节自身免疫和过敏疾病提供潜在的治疗策略。在这篇综述中，我们总结了代谢检查点及其与不同主转录因子和信号分子在 Th 亚群分化和功能中的相互作用，这可能为组织炎症和自身免疫性疾病的新型治疗干预提供思路。
