A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity

Abstract

A previously unrecognized subset of human natural killer (NK) lymphocytes is reported. These 'NK-22' cells are selectively localized in tonsil and gut mucosa and, in contrast to conventional NK cells, are poorly cytotoxic and secrete little or no interferon. Rather, they specialize in the secretion of interleukin 22 (IL-22), IL-26 and leukaemia inhibitory factor, all of which have been implicated in the protection of epithelia. The properties of NK-22 cells are consistent with an anti-inflammatory response that may contribute to the maintenance of mucosal integrity. This study identifies a subset of natural killer (NK) cells in the gut that produce interleukin-22, rather than mediate target cell killing. It is suggested that these NK cells, referred to as NK-22 cells, may help constrain inflammation and contribute to the maintenance of mucosal integrity. Natural killer (NK) cells are classically viewed as lymphocytes that provide innate surveillance against virally infected cells and tumour cells through the release of cytolytic mediators and interferon (IFN)-γ. In humans, blood CD56dim NK cells specialize in the lysis of cell targets1. In the lymph nodes, CD56bright NK cells secrete IFN-γ cooperating with dendritic cells and T cells in the generation of adaptive responses1,2. Here we report the characterization of a human NK cell subset located in mucosa-associated lymphoid tissues, such as tonsils and Peyer’s patches, which is hard-wired to secrete interleukin (IL)-22, IL-26 and leukaemia inhibitory factor. These NK cells, which we refer to as NK-22 cells, are triggered by acute exposure to IL-23. In vitro, NK-22-secreted cytokines stimulate epithelial cells to secrete IL-10, proliferate and express a variety of mitogenic and anti-apoptotic molecules. NK-22 cells are also found in mouse mucosa-associated lymphoid tissues and appear in the small intestine lamina propria during bacterial infection, suggesting that NK-22 cells provide an innate source of IL-22 that may help constrain inflammation and protect mucosal sites.