The expression levels of NKG2D and 2B4 (CD244)

are similar for dNK and pNK cells. Like CD56bright CD16neg pNK cells, dNK cells express high levels of CD94/NKG2A inhibitory receptor (see Fig. 2). One striking difference concerns the granularity level. Even if they are poorly cytotoxic, dNK cells express much larger amounts of granzyme A, granzyme B and perforin enriched cytotoxic granules than CD56dim cytotoxic pNK cells.[18, 35, 51, 54] Fine analyses of the dNK cell gene expression profile further highlighted these unique features of dNK cells with distinct properties, such as the expression of NKG2E, Ly-49L and KIR receptors, adhesion molecules, galectin-1 or some members of the tetraspan family BAY 73-4506 (CD9, CD151, CD53, CD63).[17] The precise functions of dNK cells in

Lumacaftor supplier vivo are not yet completely understood. Nonetheless, evidence exists for their pivotal contribution to the regulation of tissue homeostasis, a critical process for healthy pregnancy and optimal fetal development. At the same time, their endowment with huge plasticity and their susceptibility to external environmental stimuli should be taken into account for the success of pregnancy. Natural killer cells are named after their spontaneous and natural ability to kill tumours and virus-infected cells without previous sensitization. They belong to the group I of innate lymphoid cells because they produce large amounts of type I cytokines but not type II cytokines. They also secrete a large array of chemokines and other growth factors. In the periphery, CD56dim CD16pos pNK cells are highly cytotoxic, whereas CD56bright CD16neg NK cells are cytokine

producers. In the decidua, dNK cells are devoid of cytolytic activity. The lack of cell cytotoxicity has been linked to default in the polarization of the microtubule organizing centre to the immunological synapse or to failure of the 2B4 receptor to convey activating signals.[54, 55] However, induction of dNK cell cytotoxic function by cytokines, such as IL-15 and IL-18, or ligation of specific activating receptor suggests that the lytic machinery is Calpain tightly regulated in normal pregnancy but can be triggered by the appropriate stress signal.[49, 55, 56] Our work and other’s clearly suggest that cross-talk at the fetal–maternal interface upholds the cytotoxic function under strict control during healthy pregnancy. Inhibitory pathways involving the binding of the CD94/NKG2A inhibitory receptor to its natural ligand HLA-E expressed by the invasive fetal trophoblasts or the secretion of soluble factors such as HLA-G further comfort the tight regulation of dNK cell function during normal pregnancy.[49, 51, 57] The presence of dNK cells in the vicinity of invasive fetal trophoblasts[58] and spiral arteries is suggestive of their active contribution to trophoblast attraction, which is necessary to promote decidualization and placental development.