NK cells as recipients of cytokine signals

Cytokines are polypeptide mediators that play pivotal roles in communication between cells and can be broadly distinguished as leadered cytokines, including hematopoietins, colony stimulating factors, chemokines, tumor necrosis factor (TNF) family members, and leaderless interleukin (IL)-1 extended family, fibroblast growth factor family, high mobility group box 1 protein (HMGB1), and others. They are pleiotropic, synergistic, and redundant, conferring substantial evolutionary advantages. Cytokine expression is disturbed in many infectious, inflammatory and autoimmune disease states. Autocrine activities mediated by cytokines in natural killer (NK) cells include the roles of self-secreted interferon (IFN)γ and IL-10; paracrine mediators include the cross-talk of HMGB1, IL-12 and IL-15 between NK cells and dendritic cells (DCs) at the immunologic synapse, while endocrine activity received by NKs from release of chemokines into the vascular circulation by distant cells is vital for migration of the innate immune response from the bone marrow into the peripheral blood to an area of disease. NK cells recognize stressed cells, entertaining a constitutive ability to mediate cytotoxicity in target cells and secrete cytokines rather rapidly in response. They participate in the innate resistance to intracellular pathogens and malignancies. Their role is critical to expansion of the Th1 biased adaptive immune response and development of secondary lymphatic sites. They also influence hematopoiesis, increasing myelopoiesis and decreasing megacytopoiesis and erythropoiesis.