Ubiquitin-specific peptidase 18 (USP18) plays an important role in the development of CD11b⁺ dendritic cells (DCs) and Th17 cells, however, its role in the differentiation of other T cell subsets, especially in regulatory T (Treg) cells, is unknown. In our study, we used Usp18 KO mice to study the loss of USP18 on the impact of Treg cell differentiation and function. We found that USP18 deficiency upregulates the differentiation of Treg cells, which may lead to disrupted homeostasis of peripheral T cells, and downregulates INF-γ, IL-2, IL-17A producing CD4⁺ T cells and INF-γ producing CD8⁺ T cells. Mechanistically, we also found that the upregulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice. Finally, we found that the suppressive function of Usp18 KO Tregs is downregulated. Altogether, our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function, which may provide a new reference for the treatment of Treg function in many autoimmune diseases, and USP18 can be used as a new therapeutic target for precise medical treatment.

泛素特异性肽酶18（USP18）在CD11b ⁺树突状细胞（DCs）和Th17细胞的发育中起着重要作用，但是，在其他T细胞亚群的分化中，特别是在调节性T（Treg）细胞中，它的作用是未知。在我们的研究中，我们使用Usp18 KO小鼠研究了USP18缺失对Treg细胞分化和功能的影响。我们发现，USP18缺乏会上调Treg细胞的分化，这可能会导致外周T细胞的稳态破坏，并下调产生INF-γ，IL-2，IL-17A的CD4 ⁺ T细胞和产生INF-γ的CD8 ⁺ T细胞。从机理上讲，我们还发现Tregs的上调归因于Usp18中CD25的表达升高KO小鼠。最后，我们发现Usp18 KO Tregs的抑制功能被下调。总的来说，我们的研究是第一个鉴定USP18在Tregs分化及其抑制功能中的作用，这可能为许多自身免疫性疾病中Treg功能的治疗提供新的参考，USP18可以作为精确定位的新治疗靶标药物治疗。