QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
School of Medicine, University of Queensland, Brisbane, QLD, Australia.
Front Immunol. 2018 Nov 6;9:2578. doi: 10.3389/fimmu.2018.02578. eCollection 2018.
BTB and CNC Homology 1, Basic Leucine Zipper Transcription Factor 2 (BACH2) is a transcription factor best known for its role in B cell development. More recently, it has been associated with T cell functions in inflammatory diseases, and has been proposed as a master transcriptional regulator within the T cell compartment. In this study, we employed T cell-specific -deficient (B6. ) mice to examine the role of this transcription factor in CD4 T cell functions and in mice infected with AS. We found that under CD4 T cell polarizing conditions , Th2, and Th17 helper cell subsets were more active in the absence of expression. In mice infected with AS, although the absence of expression by T cells had no effect on blood parasitemia or disease pathology, we found reduced expansion of CD4 T cells in B6. mice, compared with littermate controls. Despite this reduction, we observed increased frequencies of Tbet IFNγ CD4 (Th1) cells and IL-10-producing Th1 (Tr1) cells in mice lacking expression by T cells. Studies in mixed bone marrow chimeric mice revealed T cell intrinsic effects of BACH2 on hematopoietic cell development, and in particular, the generation of CD4 and CD8 T cell subsets. Furthermore, T cell intrinsic BACH2 was needed for efficient expansion of CD4 T cells during experimental malaria in this immunological setting. We also examined the response of B6. mice to a second protozoan parasitic challenge with and found similar effects on disease outcome and T cell responses. Together, our findings provide new insights into the role of BACH2 in CD4 T cell activation during experimental malaria, and highlight an important role for this transcription factor in the development and expansion of T cells under homeostatic conditions, as well as establishing the composition of the effector CD4 T cell compartment during infection.
BTB 和 CNC 同源物 1，基本亮氨酸拉链转录因子 2（BACH2）是一种转录因子，以其在 B 细胞发育中的作用而闻名。最近，它与炎症性疾病中的 T 细胞功能有关，并被提议作为 T 细胞区室中的主转录调节剂。在这项研究中，我们使用 T 细胞特异性 -缺陷（B6.）小鼠来研究该转录因子在 CD4 T 细胞功能中的作用，以及在感染 AS 的小鼠中。我们发现，在 CD4 T 细胞极化条件下，缺乏 表达时，Th2 和 Th17 辅助细胞亚群更为活跃。在感染 AS 的小鼠中，尽管 T 细胞缺乏 表达对血液寄生虫血症或疾病病理学没有影响，但与同窝对照相比，我们发现 B6. 小鼠中 CD4 T 细胞的扩增减少。尽管如此，我们观察到缺乏 表达的 T 细胞中 Tbet IFNγ CD4（Th1）细胞和产生 IL-10 的 Th1（Tr1）细胞的频率增加。在混合骨髓嵌合小鼠中的研究揭示了 BACH2 在造血细胞发育中的 T 细胞内在作用，特别是 CD4 和 CD8 T 细胞亚群的产生。此外，在这种免疫背景下，实验性疟疾中 CD4 T 细胞的有效扩增需要 T 细胞内在的 BACH2。我们还检查了 B6. 对第二种原生动物寄生虫挑战的反应 感染，发现对疾病结局和 T 细胞反应有类似的影响。总之，我们的研究结果为 BACH2 在实验性疟疾中 CD4 T 细胞激活中的作用提供了新的见解，并强调了该转录因子在稳态条件下 T 细胞的发育和扩增以及建立感染期间效应性 CD4 T 细胞区室组成中的重要作用。
