1. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
2. Department of Pathology I, Spedali Civili, University of Brescia, 25123 Brescia, Italy
3. These authors contributed equally to this work.

Correspondence to: Marco Colonna¹ Correspondence and requests for materials should be addressed to M.Co. (Email: mcolonna@pathology.wustl.edu).

Abstract

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)-. In humans, blood CD56^dim NK cells specialize in the lysis of cell targets¹. In the lymph nodes, CD56^bright NK cells secrete IFN- cooperating with dendritic cells and T cells in the generation of adaptive responses^{1, 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.

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