4 research outputs found
SATB1 in Malignant T Cells
Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis
Bacterial genotoxins induce T cell senescence
Several types of pathogenic bacteria produce genotoxins that induce DNA damage in host cells. Accumulating evidence suggests that a central function of these genotoxins is to dysregulate the host's immune response, but the underlying mechanisms remain unclear. To address this issue, we investigated the effects of the most widely expressed bacterial genotoxin, the cytolethal distending toxin (CDT), on T cells—the key mediators of adaptive immunity. We show that CDT induces premature senescence in activated CD4 T cells in vitro and provide evidence suggesting that infection with genotoxin-producing bacteria promotes T cell senescence in vivo. Moreover, we demonstrate that genotoxin-induced senescent CD4 T cells assume a senescence-associated secretory phenotype (SASP) which, at least partly, is orchestrated by the ATM-p38 signaling axis. These findings provide insight into the immunomodulatory properties of bacterial genotoxins and uncover a putative link between bacterial infections and T cell senescence
Bacterial genotoxins induce T cell senescence
Several types of pathogenic bacteria produce genotoxins that induce DNA
damage in host cells. Accumulating evidence suggests that a central
function of these genotoxins is to dysregulate the host's immune
response, but the underlying mechanisms remain unclear. To address this
issue, we investigated the effects of the most widely expressed
bacterial genotoxin, the cytolethal distending toxin (CDT), on T
cells-the key mediators of adaptive immunity. We show that CDT induces
premature senescence in activated CD4 T cells in vitro and provide
evidence suggesting that infection with genotoxin-producing bacteria
promotes T cell senescence in vivo. Moreover, we demonstrate that
genotoxin-induced senescent CD4 T cells assume a senescence-associated
secretory phenotype (SASP) which, at least partly, is orchestrated by
the ATMp38 signaling axis. These findings provide insight into the
immunomodulatory properties of bacterial genotoxins and uncover a
putative link between bacterial infections and T cell senescence