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

ANDREA ZIBLAT; CAROLINA I. DOMAICA; RAUL GERMAN SPALLANZANI; XIMENA LUCIA RAFFO; LUCAS EZEQUIEL ROSSI; DAMIAN EZEQUIEL AVILA; NICOLAS I. TORRES; MERCEDES BEATRIZ FUERTES; NORBERTO W. ZWIRNER

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 APC, displays pro- and anti-inflammatory effects but its effects on human NK cells remain ill-defined. Therefore, in this work we investigated the effect of IL-27 on human NK cells. We observed that mature dendritic cells (mDC) secreted IL-27 and that blockade of IL-27R (CD130) reduced the amount of IFN-γ produced by NK cells during their co-culture, highlighting a role 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 up-regulation of CD25 and CD69 on NK cells, and displayed a synergistic effect with IL-18. Pre-incubation experiments demonstrated that IL-27 primed NK cells for IL-18-induced IFN-γ secretion which was associated with an IL-27-driven up-regulation of T-bet expression. Also, IL-27 triggered NKp46-dependent NK cell-mediated cytotoxicity against Raji, T-47D and HCT116 cells, and IL-18 enhanced this cytotoxic response. Such NK cell-mediated cytotoxicity involved up-regulation of perforin (pfp), granule exocytosis and TRAIL-mediated cytotoxicity but not Fas-FasL interaction. Moreover, IL-27 also potentiated Ab-dependent NK cell-mediated cytotoxicity (ADCC) against mAb-coated target cells. We conclude that IL-27 stimulates NK cell effector functions, which might be relevant in different physiological and pathological situations.