Role of satb1 in t cell development and differentation

Abstract

T lymphocyte development and differentiation is a multi step process that begins in the thymus and completed in the periphery Sequential development of thymocytes is dependent on T cell receptor TCR signaling and an array of transcription factors Ablation of Special AT rich binding protein 1 SATB1 blocks thymocyte development at double positive DP stage In this study we focused on understanding the role of SATB1 during thymocyte development and differentiation of T helper cell lineages Our studies using mouse thymocytes revealed that SATB1 expression coincides with T lineage commitment We found that SATB1 is upregulated in thymocytes that have undergone positive selection Interestingly CD4 and CD8 thymocytes exhibit differential expression of SATB1 owing to the strength of TCR signals they receive We show for the first time that CD4 thymocytes display bimodal expression pattern of SATB1 which we designate as SATB1Hi and SATB1Lo corresponding to distinct developmental stages Furthermore natural regulatory T cells a subset essential for maintaining immune tolerance is devoid of SATB1 expression Taken together our data suggests that SATB1 expression in developing thymocytes is regulated by TCR signaling Mature thymocytes that migrate to the periphery elicit immune responses as a function of antigenic signals Peripheral CD4 T cells upon TCR stimulation induced SATB1 expression and further inhibition of TCR signaling downregulated SATB1 expression CD4 T cells differentiate to various T helper lineages in response to antigenic signals and cytokine stimuli Our study revealed that SATB1 is upregulated during Th2 differentiation and further regulates the expression of effector cytokine genes We demonstrate that knockdown of SATB1 in Th2 cells leads to repression of effector cytokine IL4 and aberrant induction of Th1 cytokine interferon 947 Finally we show that SATB1 expression during Th2 differentiation is transcriptionally regulated by STAT6 and GATA3 Collectively these findings demonstrate that global gen