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IL‐27 stimulates human NK‐cell effector functions and primes NK cells for IL‐18 responsiveness
Author(s) -
Ziblat Andrea,
Domaica Carolina I.,
Spallanzani Raúl G.,
Iraolagoitia Ximena L. Raffo,
Rossi Lucas E.,
Avila Damián E.,
Torres Nicolás I.,
Fuertes Mercedes B.,
Zwirner Norberto W.
Publication year - 2015
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201444699
Subject(s) - perforin , interleukin 21 , microbiology and biotechnology , biology , cytotoxic t cell , downregulation and upregulation , interleukin 12 , cytotoxicity , secretion , janus kinase 3 , il 2 receptor , cd49b , lymphokine activated killer cell , interleukin 15 , granzyme , immunology , t cell , interleukin , cytokine , in vitro , immune system , endocrinology , biochemistry , gene
IL‐27, a member of the IL‐12 family of cytokines, is produced by APCs, and displays pro‐ and anti‐inflammatory effects. How IL‐27 affects human NK cells still remains unknown. In this study, we observed that mature DCs secreted IL‐27 and that blockade of IL‐27R (CD130) reduced the amount of IFN‐γ produced by NK cells during their coculture, 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 synergistic effect with IL‐18. Preincubation experiments demonstrated that IL‐27 primed NK cells for IL‐18‐induced IFN‐γ secretion, which was associated with an IL‐27‐driven upregulation 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 upregulation of perforin, granule exocytosis, and TRAIL‐mediated cytotoxicity but not Fas‐FasL interaction. Moreover, IL‐27 also potentiated Ab‐dependent cell‐mediated cytotoxicity against mAb‐coated target cells. Taken together, IL‐27 stimulates NK‐cell effector functions, which might be relevant in different physiological and pathological situations.