Lu Jingli, Liu Jiyun, Li Lulu, Lan Yan, Liang Yan
Department of Pharmacy The First Affiliated Hospital of Zhengzhou University Zhengzhou China.
Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou University Zhengzhou China.
Clin Transl Immunology. 2020 Mar 16;9(3):e1122. doi: 10.1002/cti2.1122. eCollection 2020.
Cytokines play crucial roles in orchestrating complex multicellular interactions between pancreatic β cells and immune cells in the development of type 1 diabetes (T1D) and are thus potential immunotherapeutic targets for this disorder. Cytokines that can induce regulatory functions-for example, IL-10, TGF-β and IL-33-are thought to restore immune tolerance and prevent β-cell damage. By contrast, cytokines such as IL-6, IL-17, IL-21 and TNF, which promote the differentiation and function of diabetogenic immune cells, are thought to lead to T1D onset and progression. However, targeting these dysregulated cytokine networks does not always result in consistent effects because anti-inflammatory or proinflammatory functions of cytokines, responsible for β-cell destruction, are context dependent. In this review, we summarise the current knowledge on the involvement of well-known cytokines in both the initiation and destruction phases of T1D and discuss advances in recently discovered roles of cytokines. Additionally, we emphasise the complexity and implications of cytokine modulation therapy and discuss the ways in which this strategy has been translated into clinical trials.
细胞因子在1型糖尿病（T1D）发生过程中协调胰腺β细胞与免疫细胞之间复杂的多细胞相互作用中发挥着关键作用，因此是该疾病潜在的免疫治疗靶点。能够诱导调节功能的细胞因子，如白细胞介素-10（IL-10）、转化生长因子-β（TGF-β）和白细胞介素-33（IL-33），被认为可恢复免疫耐受并预防β细胞损伤。相比之下，促进致糖尿病免疫细胞分化和功能的细胞因子，如白细胞介素-6（IL-6）、白细胞介素-17（IL-17）、白细胞介素-21（IL-21）和肿瘤坏死因子（TNF），则被认为会导致T1D的发病和进展。然而，针对这些失调的细胞因子网络并不总是能产生一致的效果，因为导致β细胞破坏的细胞因子的抗炎或促炎功能取决于具体情况。在这篇综述中，我们总结了目前关于知名细胞因子在T1D起始和破坏阶段作用的知识，并讨论了细胞因子新发现作用的研究进展。此外，我们强调了细胞因子调节治疗的复杂性和意义，并讨论了这一策略转化为临床试验的方式。
