Several studies have recently demonstrated the existence of an ITAM-dependent signaling pathway, similar to that downstream of the B cell receptor, which is triggered on human pDCs by engagement of FcεRIγ-associated membrane receptors of the C-type lectin (CLEC4C/BDCA2) or immunoglobulin (LILRA4/ILT7) super-families, and which dampens pDC cytokine responses to TLR or viral stimulations in vitro [106] [107] [108] . This regulatory pathway must be evolutionarily conserved, because some of its most specific components including BLNK and CARD11 are selectively expressed in mouse pDCs as well [28] . Indeed, the mouse SIGLECH C-type lectin receptor which associates with the ITAM-bearing adaptor DAP12 has also been shown to inhibit pDC cytokine responses to TLR stimulations [109, 110] . DAP12 functions dampen pDC cytokine production [110] , including in vivo in a cell autonomous way during CpG challenge or MCMV infection [111] . Thus, it is likely that the mouse SIGLECH receptor modulates pDC function through the triggering of the same B cell receptorlike intracellular signaling pathway as the human CLEC4C receptor, although these receptors are not orthologous. The natural ligands of human CLEC4C and mouse SIGLECH still remain to be identified. However, BST2 has been very recently identified in humans as a ligand for LILRA4. BST2 is a membrane molecule induced on many cell types by IFN-I [112] . Thus, human pDCs are uniquely equipped to sense the paracrine response to their production of IFN-I, allowing for a negative feedback loop to prevent excessive production of the cytokines that could cause deleterious effects to the host. Future studies will likely show that this is also the case in the mouse.