Laboratory of Immunobiology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Centre for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.
Immunology. 2018 Dec;155(4):418-426. doi: 10.1111/imm.12993. Epub 2018 Sep 10.
Interleukin-17 (IL-17) is a pro-inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL-17-producing γδ T cells (γδ17 cells) in addition to IL-17-producing CD4 T cells [T helper type 17 (Th17) cells] are often the main producers of IL-17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra-thymic differentiation. γδ thymocytes capable of producing IL-17, which express the transcription factor retinoic-acid-receptor-related orphan receptor γt and the signature cytokine receptor IL-23R, leave the thymus, and produce IL-17 rapidly by the stimulation with IL-1β and IL-23 in the periphery. Therefore, γδ17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. γδ T cells that can produce IL-17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL-17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of γδ17 cells in infection and inflammatory diseases and therapeutic advances targeting IL-17.
白细胞介素-17(IL-17)是一种促炎细胞因子,参与多种疾病的发生发展。最近的研究表明,除了产生白细胞介素-17 的 CD4 T 细胞(辅助性 T 细胞 17,Th17 细胞)外,产生白细胞介素-17 的 γδ T 细胞(γδ17 细胞)通常是炎症性疾病小鼠模型中白细胞介素-17 的主要产生者。γδ T 细胞在胸腺内分化过程中具有功能特异性。能够产生白细胞介素-17 的 γδ 胸腺细胞表达转录因子维甲酸受体相关孤儿受体γt 和特征性细胞因子受体白细胞介素-23R,离开胸腺后,在外周受到白细胞介素-1β 和白细胞介素-23 的刺激,迅速产生白细胞介素-17。因此,γδ17 细胞在宿主防御病原体和炎症性疾病的早期阶段发挥重要作用。银屑病患者的皮肤和强直性脊柱炎患者的外周血中也增加了能够产生白细胞介素-17 的 γδ T 细胞。事实上,靶向白细胞介素-17 的治疗方法已被批准或正在临床试验中,并已被证明对治疗银屑病、银屑病关节炎和强直性脊柱炎非常有效。在这篇综述中,我们讨论了 γδ17 细胞在感染和炎症性疾病中的病理生理功能的最新知识,以及靶向白细胞介素-17 的治疗进展。