Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Cell Mol Immunol. 2023 Sep;20(9):1002-1022. doi: 10.1038/s41423-023-01036-7. Epub 2023 May 23.
Balanced immunity is pivotal for health and homeostasis. CD4 helper T (Th) cells are central to the balance between immune tolerance and immune rejection. Th cells adopt distinct functions to maintain tolerance and clear pathogens. Dysregulation of Th cell function often leads to maladies, including autoimmunity, inflammatory disease, cancer, and infection. Regulatory T (Treg) and Th17 cells are critical Th cell types involved in immune tolerance, homeostasis, pathogenicity, and pathogen clearance. It is therefore critical to understand how Treg and Th17 cells are regulated in health and disease. Cytokines are instrumental in directing Treg and Th17 cell function. The evolutionarily conserved TGF-β (transforming growth factor-β) cytokine superfamily is of particular interest because it is central to the biology of both Treg cells that are predominantly immunosuppressive and Th17 cells that can be proinflammatory, pathogenic, and immune regulatory. How TGF-β superfamily members and their intricate signaling pathways regulate Treg and Th17 cell function is a question that has been intensely investigated for two decades. Here, we introduce the fundamental biology of TGF-β superfamily signaling, Treg cells, and Th17 cells and discuss in detail how the TGF-β superfamily contributes to Treg and Th17 cell biology through complex yet ordered and cooperative signaling networks.
平衡的免疫对于健康和内稳态至关重要。CD4 辅助 T（Th）细胞是免疫耐受和免疫排斥之间平衡的核心。Th 细胞采用不同的功能来维持耐受和清除病原体。Th 细胞功能的失调常常导致疾病，包括自身免疫、炎症性疾病、癌症和感染。调节性 T（Treg）和 Th17 细胞是参与免疫耐受、内稳态、致病性和病原体清除的关键 Th 细胞类型。因此，了解 Treg 和 Th17 细胞在健康和疾病中的调节机制至关重要。细胞因子在指导 Treg 和 Th17 细胞功能方面起着重要作用。进化上保守的 TGF-β（转化生长因子-β）细胞因子超家族特别引人注目，因为它是 Treg 细胞（主要具有免疫抑制作用）和 Th17 细胞（可以是促炎、致病性和免疫调节性）生物学的核心。TGF-β 超家族成员及其复杂的信号通路如何调节 Treg 和 Th17 细胞功能是一个已经被深入研究了二十年的问题。在这里，我们介绍 TGF-β 超家族信号、Treg 细胞和 Th17 细胞的基本生物学，并详细讨论 TGF-β 超家族如何通过复杂但有序和协作的信号网络促进 Treg 和 Th17 细胞生物学。
