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Bartmann, J. ; Frankenberger, M. ; Neurohr, C.* ; Eickelberg, O. ; Nößner, E. ; von Wulffen, W.

A novel role of MMP-13 for murine DC function: Its inhibition dampens T cell activation.

Int. Immunol. 28, 473-487 (2016)

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Dendritic cells (DC) have been shown to express Matrix Metalloproteinase-13 (MMP-13), but little is known about its specific function in DCs and its role in inflammatory conditions. In the present study, we describe a novel role of MMP-13 in regulating the immunostimulatory function of murine DCs through moderating MHC-I surface presentation, endocytosis, and cytokine/chemokine secretion. MMP-13 expression was confirmed in bone marrow-derived DCs at mRNA and protein level and, furthermore, on activity level. Remarkably, LPS treatment strongly enhanced MMP-13 mRNA expression as well as MMP-13 activity, indicating an important role of MMP-13 in inflammatory processes. Functionally, MMP-13 inhibition did not influence DC migratory capacity, while endocytosis of OVA was significantly decreased. Inhibition of MMP-13 lowered the capability of murine DCs to activate CD8(+) T cells, apparently through reducing MHC-I surface presentation. Decreased surface expression of CD11c on DCs, as well as changes in the DC cytokine/chemokine profile after MMP-13 inhibition, emphasize the influence of MMP-13 on DC function. Moreover, T cell targeting cytokines such as IL-12, IL-23, and IL-6 were significantly reduced. Collectively, our data reveal a novel involvement of MMP-13 in regulating DC immunobiology through moderating MHC-I surface presentation, endocytosis, and cytokine/chemokine secretion. Furthermore, the reduced MHC-I surface presentation by DCs resulted in a poor CD8(+) T cell response in vitro. This novel finding indicates that MMP-13 might be a promising target for therapeutic intervention in inflammatory diseases.

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