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 Bach2 -deficient (B6. Bach2 Δ T ) mice to examine the role of this transcription factor in CD4 + T cell functions in vitro and in mice infected with Plasmodium chabaudi AS. We found that under CD4 + T cell polarizing conditions in vitro , Th2, and Th17 helper cell subsets were more active in the absence of Bach2 expression. In mice infected with P. chabaudi AS, although the absence of Bach2 expression by T cells had no effect on blood parasitemia or disease pathology, we found reduced expansion of CD4 + T cells in B6. Bach2 Δ T 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 Bach2 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. Bach2 Δ T mice to a second protozoan parasitic challenge with Leishmania donovani 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.
【저자키워드】 Inflammation, T cells, malaria, Protozoan, BACH2,