Natural killer (NK) cells are innate lymphoid cells capable to recognize and spontaneously eliminate infected, damaged or malignant transformed cells without prior sensitization. Reactivity of NK cells towards their targets depends on the integration of all signals transmitted by their large repertoire of activating and inhibitory receptors. This ultimately tightly regulates NK-cell behavior. Beyond their capacity to “kill” NK cells can produce various soluble factors and interact with other immune cells to shape immune responses. Their role in virus and tumor surveillance is well established. However, their role in allo-responses in transplantation remains somewhat elusive. Accumulating data suggest a key role of NK cells mediated graft damage in kidney transplantation that represents probably the most documented case. A better understanding of NK cells functions in allo-immune context may offer new therapeutic targets.

The aim of this Research Topic is to provide a comprehensive overview of the current knowledge related to the behavior and the role of NK cells in organ transplantation and graft rejection. NK cells are able to directly regulate T cells responses and to kill highly activated T cells. In addition, dendritic cell-natural killer cell crosstalk modulates T cell activation. NK cells may promote allograft tolerance by killing allogeneic antigen presenting cells. However, “Missing self” and donor specific antibodies (DSA) can induce NK cell activation and trigger chronic rejection in kidney transplantation. These data raise a fundamental question: are NK cells protective or pathogenic in allo-immune responses? A deep knowledge of this facet of NK cells immune functions may allow to target/manipulate these cells to improve the therapeutic management of graft rejections.

We welcome contributions as Original Research or Review around the following subjects in fundamental, translational, and clinical settings:

• Profiling of NK cells in allo-immune responses in transplantation

• Characterization of NK cell interactions with other immune cells to shape allo-immune responses

• Mechanisms explaining NK cells “behavior”/responses in the context of allo-immune responses.

• Experimental models of graft rejection allowing a deep comprehension of the role of NK cells in allo-immune responses

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.

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NK Cells in Transplantation