Possible mechanism of shedding of BAFF in human T cells (129.2)

Abstract

B cell activating factor of the TNF family, or BAFF, is a type II membrane-bound protein and the extracellular C-terminal fragment is released from the cells as soluble BAFF (sBAFF). BAFF is mainly produced in monocytes and dendritic cells, and regulates proliferation, differentiation, and survival of B cells. Our recent study has revealed that the expression of BAFF is abnormally elevated in peripheral T cells of SLE patients, suggesting that BAFF plays an important role in the pathogenesis of autoimmune diseases. In the present study, we investigated the expression of BAFF in T cells of Sjögren’s syndrome (SS), and found that the expression of BAFF was enhanced in peripheral T cells of SS patients upon stimulation. We further analyzed the mechanism of release of sBAFF from T cells, since this step may provide a therapeutic possibility to treat the diseases. Particularly, we focused on furin and matrix metalloproteinases, which are membrane bound proteases and responsible for shedding of several proteins. Investigation with specific inhibitors against these proteases revealed that at least furin and MMP9 was involved in the release of sBAFF.