Natural killer receptors: the burden of a name

Abstract

A population of cells that expresses the NK cell receptor NKp46 and produces interleukin (IL)-22 have recently attracted considerable attention. The identity of these cells is still the subject of speculation, being variably defined as a novel NK cell subset or as a population containing conventional NK (cNK) cell precursors. In this issue, two studies shed light on this conundrum, demonstrating that NKp46(+) IL-22(+) cells and cNK cells belong to distinct lineages.

Figure 1.

NCR22 and conventional NK cells have different function and ontogeny. NCR22 and cNK cells home to mucosal sites and mucosal-associated lymphoid tissues. Upon interaction with microbial components, mucosal dendritic cells produce IL-23, which stimulates NCR22 cells to secrete IL-22, which is believed to protect the mucosa and control inflammation. In response to dendritic cell-derived cytokines such as IL-1, IL-12, and IL-18, cNK cells produce IFN-γ, perforin and granzymes, which target pathogen infected cells. In the absence of helix-loop-helix inhibitor Id2, both NCR22 and conventional NK cells fail to develop. However, the development of these cell types differs in its dependency on IL-7, IL-15, Rorγt and E4BP4.