In contrast to our ever increasing knowledge regarding the role of CD137 signaling in the induction and development of adaptive immunity, our understanding with regard to the effect of CD137 in innate immunity is still in it's earliest stages. Experimental evidence supports that CD137 engagement is capable of triggering activity of natural killer (NK) cells, macrophages, dendritic cells (DC), and granulocytes. The majority of results, however, are obtained in cell culture systems which raise the questions regarding their roles in ongoing immune responses in vivo and in human diseases. The hypothesis that is presently being pushed forward is that the CD137 pathway plays a critical role in the regulation of innate immunity and may bridge innate and adaptive immunity. This chapter will assemble available data with an attempt to delineate the functions of CD137 in individual components of innate immunity.

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