Department of Surgery, Center for Immunobiology and Transplantation Research, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas USA.
Burns Trauma. 2014 Jan 26;2(1):11-7. doi: 10.4103/2321-3868.124771. eCollection 2014.
The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune tolerance, followed by discussing other cytokines that maintain immune tolerance through inducing CD4(+)Foxp3(+) regulatory T cells (Tregs), which negatively control immune cells. Interleukin (IL)-2 is the most potent cytokine in promoting the development and survival of Tregs, thereby mediating immune tolerance. IL-35 is mainly produced by Tregs, but its biology function remains to be defined. Finally, we discuss the actions of proinflammatory cytokines that breach immune tolerance and induce autoimmunity, which include IL-7, IL-12, IL-21, and IL-23. Recent genetic studies have revealed the role of these cytokines (or their cognate receptors) in susceptibility to autoimmune diseases. Taken together, we highlight in this review the cytokine regulation of immune tolerance, which will help in further understanding of human diseases that are caused by dysregulated immune system.
免疫系统提供抵御入侵病原体的防御机制，同时对自身抗原保持免疫耐受。这种免疫稳态通过免疫细胞与细胞因子环境之间的直接相互作用来协调，免疫细胞在其中发育和发挥功能。在此，我们讨论了细胞因子维持或打破免疫耐受的三个非冗余范例。我们首先描述了抗炎细胞因子如何通过直接抑制免疫细胞来发挥作用，从而强制免疫耐受，然后讨论了通过诱导 CD4(+)Foxp3(+)调节性 T 细胞（Tregs）来维持免疫耐受的其他细胞因子，Tregs 通过负向控制免疫细胞来发挥作用。白细胞介素（IL）-2 是促进 Tregs 发育和存活的最有效细胞因子，从而介导免疫耐受。IL-35 主要由 Tregs 产生，但它的生物学功能仍有待确定。最后，我们讨论了打破免疫耐受并诱导自身免疫的促炎细胞因子的作用，包括 IL-7、IL-12、IL-21 和 IL-23。最近的遗传研究揭示了这些细胞因子（或其同源受体）在自身免疫性疾病易感性中的作用。总之，我们在这篇综述中强调了细胞因子对免疫耐受的调节作用，这将有助于进一步了解由免疫系统失调引起的人类疾病。
