title: IL-27 driven upregulation of surface HLA-E expression on monocytes inhibits IFN-γ release by autologous NK cells.
abstract: HLA-G and HLA-E are HLA-Ib molecules with several immunoregulatory properties. Their cell surface expression can be modulated by different cytokines. Since IL-27 and IL-30 may either stimulate or regulate immune responses, we have here tested whether these cytokines may modulate HLA-G and -E expression and function on human monocytes. Monocytes expressed gp130 and WSX-1, the two chains of IL27 receptor (R), and IL6Rα (that serves as IL-30R, in combination with gp130). However, only IL27R appeared to be functional, as witnessed by IL-27 driven STAT1/ STAT3 phosphorylation. IL-27, but not IL-30, significantly upregulated HLA-E (but not HLA-G) expression on monocytes. IFN-γ; secretion by activated NK cells was dampened when the latter cells were cocultured with IL-27 pretreated autologous monocytes. Such effect was not achieved using untreated or IL-30 pretreated monocytes, thus indicating that IL-27 driven HLA-E upregulation might be involved, possibly through the interaction of this molecule with CD94/NKG2A inhibitory receptor on NK cells. In contrast, cytotoxic granules release by NK cell in response to K562 cells was unaffected in the presence of IL-27 pretreated monocytes. In conclusion, we delineated a novel immunoregulatory function of IL-27 involving HLA-E upregulation on monocytes that might in turn indirectly impair some NK cell functions.
authors.affiliation: Laboratory of Oncology, Istituto Giannina Gaslini, Via Gaslini 1, 16148 Genova, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Morandi
authors.affiliation: Laboratory of Oncology, Istituto Giannina Gaslini, Via Gaslini 1, 16148 Genova, Italy.
authors.forename: Irma
authors.initials: I
authors.lastname: Airoldi
authors.affiliation: Laboratory of Oncology, Istituto Giannina Gaslini, Via Gaslini 1, 16148 Genova, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
mesh_terms: D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000187:drug effects*; D059951:HLA-G Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D000097625:HLA-E Antigens
chemical_list: D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D007378:Interleukins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human; C464565:MYDGF protein, human; C494079:STAT1 protein, human; C494086:STAT3 protein, human
references.citation: Eur J Immunol. 2001 Oct;31(10):2926-35
references.pmid: 11592068
references.citation: J Biol Chem. 2001 Mar 2;276(9):6133-9
references.pmid: 11087747
references.citation: Blood. 2007 Apr 1;109(7):2806-14
references.pmid: 17179229
references.citation: Nat Immunol. 2010 Dec;11(12):1119-26
references.pmid: 21057510
references.citation: J Immunol. 2014 Mar 15;192(6):2634-42
references.pmid: 24554774
references.citation: J Immunol. 1996 Jun 1;156(11):4224-31
references.pmid: 8666791
references.citation: Bone Marrow Transplant. 2009 May;43(9):693-9
references.pmid: 19011664
references.citation: Rheumatology (Oxford). 2011 May;50(5):966-72
references.pmid: 21186170
references.citation: Semin Cancer Biol. 2007 Dec;17(6):469-79
references.pmid: 17825579
references.citation: J Leukoc Biol. 2009 Dec;86(6):1295-303
references.pmid: 19801497
references.citation: Res Immunol. 1996 Jun;147(5):301-13
references.pmid: 8876058
references.citation: Immunity. 2002 Jun;16(6):779-90
references.pmid: 12121660
references.citation: J Biol Chem. 2010 Aug 6;285(32):24404-11
references.pmid: 20519510
references.citation: Immunity. 2003 Nov;19(5):641-4
references.pmid: 14614851
references.citation: J Immunol. 2006 Sep 1;177(5):3100-7
references.pmid: 16920947
references.citation: Int Immunol. 1999 May;11(5):803-11
references.pmid: 10330285
references.citation: J Leukoc Biol. 2011 May;89(5):729-34
references.pmid: 21330353
references.citation: J Biol Chem. 1996 Aug 16;271(33):20035-46
references.pmid: 8702722
references.citation: Iran Biomed J. 2011;15(1-2):1-5
references.pmid: 21725493
references.citation: Immunology. 2009 Sep;128(1 Suppl):e816-25
references.pmid: 19740343
references.citation: Immunogenetics. 2003 Feb;54(11):767-75
references.pmid: 12618909
references.citation: J Clin Invest. 2002 Nov;110(10):1515-23
references.pmid: 12438449
references.citation: F1000 Biol Rep. 2009 Sep 08;1:70
references.pmid: 20948617
references.citation: J Biol Chem. 2013 Feb 8;288(6):4346-54
references.pmid: 23209286
references.citation: J Immunol. 1999 Dec 1;163(11):6301-5
references.pmid: 10570324
references.citation: Eur J Immunol. 2012 Jun;42(6):1547-52
references.pmid: 22678908
references.citation: Cell Mol Life Sci. 1999 Mar;55(3):327-33
references.pmid: 10228553
references.citation: Eur J Immunol. 2000 Jun;30(6):1623-31
references.pmid: 10898498
references.citation: Cancer. 2001 Jul 15;92(2):369-76
references.pmid: 11466692
references.citation: PLoS One. 2011;6(10):e26173
references.pmid: 22039443
references.citation: J Exp Med. 1998 Mar 2;187(5):813-8
references.pmid: 9480992
references.citation: Nature. 2000 Oct 19;407(6806):916-20
references.pmid: 11057672
references.citation: Science. 2000 Feb 11;287(5455):1031
references.pmid: 10669413
references.citation: J Immunol. 2012 Jan 15;188(2):864-73
references.pmid: 22156348
references.citation: Am J Pathol. 2001 Sep;159(3):817-24
references.pmid: 11549573
references.citation: Immunol Rev. 1998 Jun;163:129-38
references.pmid: 9700506