IL-23 modulates CD56+/CD3- NK cell and CD56+/CD3+ NK-like T cell function differentially from IL-12.
NK and NK-like T cells play an essential role in linking innate and adaptive immunity through their ability to secrete IFN-gamma. The exact trigger initiating production of IFN-gamma is uncertain. Antigen-presenting cell (APC)-derived IL-12 is thought to be the classical IFN-gamma-inducing cytokine but requires an additional stimulus such as IFN-gamma itself. IL-23 and IL-18 are among the first cytokines secreted by APC in response to binding of pathogen-associated molecular patterns such as LPS. Thus, early APC-derived IL-23 may be an initial trigger of IFN-gamma production in NK and NK-like T cells. Herein, we characterized the effect of IL-23 on IFN-gamma secretion by NK and NK-like T cells. Our findings show that IL-23 and IL-18 synergistically elicit IFN-gamma production in NK-like T cells but not in NK cells. In contrast, IL-12 together with IL-18-induced secretion of IFN-gamma in both populations. The observed synergy between IL-23 and IL-18 in NK-like T cells coincided with IL-23-mediated up-regulation of IL-18Ralpha. Furthermore, IL-23 up-regulated CD56 expression in NK-like T cells and, together with IL-18, induced proliferation of NK and NK-like T cells. We postulate a role for APC-derived IL-23 in the activation of NK and NK-like T cells early in infection and in shaping T(h)1 differentiation, via induction of IFN-gamma, which provides the additional stimulus needed for APC to subsequently produce IL-12.
van de Wetering
Diederik
D
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
de Paus
Roelof A
RA
van Dissel
Jaap T
JT
van de Vosse
Esther
E
D017252:CD3 Complex; D019002:CD56 Antigen / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D004357:Drug Synergism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D018189:Immunomagnetic Separation; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D017252:CD3 Complex; D019002:CD56 Antigen; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D053759:Interleukin-23; D018664:Interleukin-12; D007371:Interferon-gamma