Abstract
Abstract HLA-B-associated transcript 3 (BAT3) also known as Scythe or BAG6, is a nuclear protein that has recently been implicated in the control of apoptosis and in NK-DC cell cross-talk. Here, we demonstrate that BAT3 modulates the immune response by regulating the function of macrophages and dendritic cells. BAT3 is secreted by macrophages and dendritic cells in vitro and extracellular BAT3 down-regulates the production of nitric oxide and proinflammatory cytokines in IFN-γ and LPS stimulated macrophages. Extracellular BAT3 also down-regulates the LPS-stimulated maturation of dendritic cells. The immunodominant Mycobacterium tuberculosis antigen ESAT-6 (early secreted antigenic target-6) up-regulates BAT3 expression in macrophages and dendritic cells in vitro. Intracellular BAT3 regulates ESAT-6 induced apoptosis of macrophages by interacting with the anti-apoptotic protein BCL-2 (B-cell lymphoma 2) indicating that BAT3 may play a role in pathogenesis of tuberculosis. Taken together, the data suggest that BAT3 may exert different immunomodulatory regulations depending on whether it is intra-or extracellular.
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