The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that 
has been implicated in various aspects of adaptive and innate immune responses. 
Nevertheless, the role of CYLD in the function of specific types of immune cells 
remains elusive. In this report we have used conditional gene targeting in mice 
to address the role of the deubiquitinating activity of CYLD in the 
myelomonocytic lineage. Truncation of the deubiquitinating domain of CYLD 
specifically in myelomonocytic cells impaired the development of lethal 
LPS-induced endotoxic shock and the accumulation of thioglycollate-elicited 
peritoneal macrophages. Our data establish CYLD as a regulator of 
monocyte-macrophage activation in response to inflammatory stimuli and identify 
it as a potential target for therapeutic intervention in relevant inflammatory 
disorders in humans.