美国麻省理工学院Vijay K. Kuchroo等近期取得重要工作进展，他们研究发现Th1样细胞中结肠炎表型的诱导依赖于白细胞介素-23受体信号传导。相关论文于2022年9月6日在线发表于《免疫》杂志上。

研究人员报告了在体外用IL-12 + IL-21分化的Th1样细胞，显示出与使用eGFP报告小鼠的致病性Th17细胞相似的IL-23R表达。命运图确定这些细胞在成为Th1样细胞之前没有通过Th17细胞状态转变，在T细胞过继转移结肠炎模型中观察到它们在体内的出现。使用IL-23R缺陷型Th1样细胞，研究人员证明了IL-23R是高度结肠炎表型发展所必需的。

肠道T细胞的单细胞RNA测序分析鉴定了Th1样细胞中的IL-23R依赖性基因，这些基因与Th17细胞中表达的基因不同。Th1样细胞中调节因子之一（CD160）的扰动抑制了结肠炎的发生。因此，研究人员将推翻了IL-23R作为单纯的Th17细胞特异性因子的观点，认为IL-23R信号转导也是诱导组织炎症的Th1样细胞的致病驱动因素。

据介绍，白细胞介素-23受体在诱导炎症和自身免疫中起关键作用。

附：英文原文

Title: Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling

Author: Mathias Pawlak, David DeTomaso, Alexandra Schnell, Gerd Meyer zu Horste, Youjin Lee, Jackson Nyman, Danielle Dionne, Brianna M.L. Regan, Vasundhara Singh, Toni Delorey, Markus A. Schramm, Chao Wang, Antonia Wallrapp, Patrick R. Burkett, Samantha J. Riesenfeld, Ana C. Anderson, Aviv Regev, Ramnik J. Xavier, Nir Yosef, Vijay K. Kuchroo

Issue&Volume: 2022-09-06

Abstract: Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity.Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cellsusing eGFP reporter mice. Fate mapping established that these cells did not transitionthrough a Th17 cell state prior to becoming Th1-like cells, and we observed theiremergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells,we demonstrated that IL-23R was required for the development of a highly colitogenicphenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependentgenes in Th1-like cells that differed from those expressed in Th17 cells. The perturbationof one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis.We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23Rsignaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.

DOI: 10.1016/j.immuni.2022.08.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00400-9