1,720,986 research outputs found

    Main NK cell receptors and their ligands: regulation by microRNAs

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    The NK cells functions are finely tuned by several kinds of inhibitory and activating receptors, whose pattern of expression characterizes different NK subpopulations and varies with the cell activation status. MicroRNAs have an important role in tightly regulating the expression of NK receptors and, analogously, the expression of their ligands in target cells. The relevance of the microRNA-mediated control is highlighted by the dysregulation of these pathways observed in cancer and virus-infected cells. Here we review our current knowledge of the microRNAs involved in the regulation of NK receptors, as well as that of the corresponding cellular ligands

    IL-12 or IL-4 prime human NK cells to mediate functionally divergent interactions with dendritic cells or tumors

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    In the course of inflammatory responses in peripheral tissues, NK cells may be exposed to cytokines such as IL-12 and IL-4 released by other cell types that may influence their functional activities. In the present study we comparatively analyzed purified human peripheral blood NK cells that had been exposed to either IL-12 or IL-4 during short (overnight) incubation. We show that although IL-12-cultured NK cells produced abundant IFN-gamma, TNF-alpha, and GM-CSF in response to stimuli acting on the NKp46-activating receptor, IL-4-cultured NK cells did not release detectable levels of these cytokines. In contrast, IL-4-cultured NK cells produced significant levels of TNF-alpha and GM-CSF only when stimulated with PMA and ionomycin. In no instance could the production of IL-5 and IL-13 be detected. Importantly, IL-12-cultured, but not IL-4-cultured, NK cells displayed strong cytolytic activity against various tumor cells or immature dendritic cells (DCs). Moreover, only NK cells that had been cultured in IL-12 were able to induce substantial DC maturation. Our data suggest that NK cells exposed to IL-12 for a time interval compatible with in vivo responses may favor the selection of appropriate mature DCs for subsequent Th1 cell priming in secondary lymphoid organs. On the contrary, NK cells exposed to IL-4 do not exert DC selection, may impair efficient Th1 priming, and favor either tolerogenic or Th2-type responses

    Human NK cells and NK receptors

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    In early seventies "natural killer (NK) cells", a third lymphocyte subset was discovered that revealed an unexpected ability to kill syngeneic and allogeneic tumor targets, thus emerging as the most potent non-specific cytotoxic cells in both human and mouse. Decades of research revealed the multifaceted nature of these cells. Now we know that NK cells are highly specific cells able to discriminate between self (which is spared) and non-self (which is attacked). Most of the specific and non HLA-specific surface receptors involved in NK cell recognition and function have been identified and, to date, only few of them still remain orphans. We also know that NK cells contribute to both innate and adaptive immune responses, interact with other immune cell types and release type 1 cytokines and chemokines. Moreover, fundamental data are accumulating on NK cell development and migration under both physiological and pathological conditions. The time is arrived to exploit these cells in the cure of cancer patients. While encouraging results emerged in hematological malignances, the road to treat solid tumors using NK cells is still covered by obstacles that hamper their function and that just begin to be unveiled
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