Department of Immunology, the Fourth Military Medical University, Xi'an 710032, China; Department of Immunology, Xi'an Medical University, No.1, Xinwang Road, Xi'an 710021, China.
Department of Immunology, the Fourth Military Medical University, Xi'an 710032, China; Medical College of Yan'an University, No.580, Shengdi Road, Yan'an 716000, China; Department of Neurology, Xianyang Hospital of Yan'an University, No.38, Wenlin Road, Xianyang 712000, China.
Mol Immunol. 2021 Apr;132:192-198. doi: 10.1016/j.molimm.2021.01.002. Epub 2021 Jan 13.
T regulatory type 1 (Tr1) cells act as a key regulator in maintaining peripheral immune tolerance. Several costimulatory molecules for T cells have been identified in Tr1 cells, but their intrinsic functions are still unclear. Here we showed CD226 was highly expressed in Tr1 cells. CD226-deficient Tr1 cells were defective in proliferation and sensitive to apoptosis. In addition, CD226-deficient Tr1 cells showed lower inhibitory capacity of T cell proliferation and reduced IL-10 production. CD226 deficiency also inhibited Tr1 cell differentiation in vitro. When stimulated with IL-2, CD226-deficient Tr1 cells showed impaired STAT5 signaling. Therefore, our data suggest CD226 might play an important role in Tr1 cell homeostasis, function and differentiation. This study facilitates further biological characterization of this regulatory T cell subset.
调节性 T 细胞 1 型(Tr1)作为维持外周免疫耐受的关键调节剂。已经在 Tr1 细胞中鉴定出几种 T 细胞的共刺激分子,但它们的内在功能仍不清楚。在这里,我们发现 CD226 在 Tr1 细胞中高度表达。CD226 缺陷的 Tr1 细胞增殖缺陷,并对细胞凋亡敏感。此外,CD226 缺陷的 Tr1 细胞对 T 细胞增殖的抑制能力降低,IL-10 产生减少。CD226 缺陷也抑制了体外 Tr1 细胞的分化。当用 IL-2 刺激时,CD226 缺陷的 Tr1 细胞显示出 STAT5 信号受损。因此,我们的数据表明 CD226 可能在 Tr1 细胞的稳态、功能和分化中发挥重要作用。本研究促进了对该调节性 T 细胞亚群的进一步生物学特征的研究。