IL-27 stimulates human NK-cell effector functions and primes NK cells for IL-18 responsiveness

ZIBLAT, ANDREA; DOMAICA, CAROLINA INÉS; SPALLANZANI, RAÚL GERMÁN; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; ROSSI, LUCAS EZEQUIEL; ÁVILA, DAMIÁN EZEQUIEL; TORRES, NICOLÁS IGNACIO; FUERTES, MERCEDES BEATRIZ; ZWIRNER, NORBERTO WALTER

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2015 vol. 45 p. 192 - 202

0014-2980

IL-27, a member of the IL-12 family of cytokines, is produced by APCs, and displayspro- and anti-inflammatory effects. How IL-27 affects human NK cells still remainsunknown. In this study, we observed that mature DCs secreted IL-27 and that blockadeof IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during theircoculture, showing the importance of IL-27 during DC?NK-cell crosstalk. Accordingly,human rIL-27 stimulated IFN-γ secretion by NK cells in a STAT1-dependent manner,induced upregulation of CD25 and CD69 on NK cells, and displayed a synergisticeffect with IL-18. Preincubation experiments demonstrated that IL-27 primed NK cellsfor IL-18-induced IFN-γ secretion, which was associated with an IL-27-driven upregulationof T-bet expression. Also, IL-27 triggered NKp46-dependent NK-cell-mediatedcytotoxicity against Raji, T-47D, and HCT116 cells, and IL-18 enhanced this cytotoxicresponse. Such NK-cell-mediated cytotoxicity involved upregulation of perforin, granuleexocytosis, and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover,IL-27 also potentiated Ab-dependent cell-mediated cytotoxicity against mAb-coated targetcells. Taken together, IL-27 stimulates NK-cell effector functions, which might berelevant in different physiological and pathological situations