NK Cells in Human Diseases: Friends or Foes?

NK cells are lymphocytes of the innate immune system well known for their importance to control viral infections and tumor development, but also intracellular bacterial and parasitic infections. A balance between negative and positive signals transmitted via germ line-encoded inhibitory and activating receptors controls the function of NK cells. Activated NK cells respond by killing the infected or tumor cells without prior sensitization, and by producing cytokines and chemokines. It has been shown that NK cells cross-talk with other immune cells such as dendritic cells and can shape the adaptive immune response through these cross-talks as well as by their cytokine/chemokine production. NK cells can also regulate the immune response by killing other immune cells like overactivated T cells or by producing antiinflammatory cytokines when the inflammatory response is too strong to try to minimize possible off target effects. However NK cells are not friends in all situations. Indeed, it has been shown in LCMV-infected murine models that depending on the viral inoculation load NK cells can help fight the infection helping animal survival or can induce the development of a chronic infection. Moreover in animal cancer models, it has been shown that NK cells can kill anti-tumoral T cells, and recent studies following patients has begun to confirm these findings in some type of human cancers. Other studies implicate NK cells in contributing to both graft rejection and tolerance to an allograft. Furthermore, the involvement of NK cells in some autoimmune diseases like rheumatoid arthritis is not fully elucidated.

The scope of this Research Topic is to present and discuss the actual knowledge on the role of NK cells in human diseases: viral infections as well as other infections, cancer responses, transplantation and autoimmunity. Which are the NK cell subsets that play a role in these diseases? Is there a different phenotype between protective NK cells (antiviral, antitumoral) and NK cells involved in disease pathogenesis? How are these diverse NK cells activated and do they function primarily through direct cytotoxicity, ADCC or cytokine and chemokine production? What are the signals or interactions that can change and shape the NK cell response shifting them from protective to harmful?

We welcome the community to submit reviews on historical aspects and current findings, original research manuscripts, as well as theories and methods to better study these questions, with the aim that this will help the community to determine what could be the main future research directions to better understand the role of NK cells in human disease protection or development.