title: IL-3 synergises with basophil-derived IL-4 and IL-13 to promote the alternative activation of human monocytes.
abstract: Basophil-derived IL-4 is involved in the alternative activation of mouse monocytes, as recently shown in vivo. Whether this applies to human basophils and monocytes has not been established yet. Here, we sought to characterise the interaction between basophils and monocytes and identify the molecular determinants. A basophil-monocyte co-culture model revealed that IL-3 and basophil-derived IL-4 and IL-13 induced monocyte production of CCL17, a marker of alternative activation. Critically, IL-3 and IL-4 acted directly on monocytes to induce CCL17 production through histone H3 acetylation, but did not increase the recruitment of STAT5 or STAT6. Although freshly isolated monocytes did not express the IL-3 receptor α chain (CD123), and did not respond to IL-3 (as assessed by STAT5 phosphorylation), the overnight incubation with IL-4 (especially if associated with IL-3) upregulated CD123 expression. IL-3-activated JAK2-STAT5 pathway inhibitors reduced the CCL17 production in response to IL-3 and IL-4, but not to IL-4 alone. Interestingly, monocytes isolated from allergen-sensitised asthmatic patients exhibited a higher expression of CD123. Taken together, our data show that the JAK2-STAT5 pathway modulates both basophil and monocyte effector responses. The coordinated activation of STAT5 and STAT6 may have a major impact on monocyte alternative activation in vitro and in vivo.
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.|Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Borriello
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Longo
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Spinelli
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pecoraro
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.|Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: Francescopaolo
authors.initials: F
authors.lastname: Granata
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.|Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: Rosaria Ilaria
authors.initials: RI
authors.lastname: Staiano
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.|Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Loffredo
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.|Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Spadaro
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.|Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Beguinot
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, USA.
authors.forename: John
authors.initials: J
authors.lastname: Schroeder
authors.affiliation: Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.|Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Marone
mesh_terms: D001491:Basophils / Q000276:immunology*; D015153:Blotting, Western; D054414:Chemokine CCL17 / Q000096:biosynthesis; D047369:Chromatin Immunoprecipitation; D018920:Coculture Techniques / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology*; D007377:Interleukin-3 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C106230:CCL17 protein, human; D054414:Chemokine CCL17; C578095:IL13 protein, human; C508596:IL3 protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; D007377:Interleukin-3; D015847:Interleukin-4
keywords: Allergy; Basophils; CCL17; JAK-STAT; Monocytes
references.citation: J Dermatol. 2003 Jan;30(1):26-32
references.pmid: 12598706
references.citation: J Immunol. 2004 Jun 15;172(12):7734-43
references.pmid: 15187157
references.citation: J Exp Med. 1994 Apr 1;179(4):1109-18
references.pmid: 8145033
references.citation: J Immunol. 1994 Aug 15;153(4):1808-17
references.pmid: 7519213
references.citation: Cytokine. 1994 Jul;6(4):407-13
references.pmid: 7948749
references.citation: Cytokine. 1996 Jun;8(6):476-81
references.pmid: 8818544
references.citation: Cytokine. 1998 Jul;10(7):487-94
references.pmid: 9702411
references.citation: J Clin Invest. 1999 Oct;104(8):1097-105
references.pmid: 10525048
references.citation: Eur J Immunol. 2006 Jul;36(7):1882-91
references.pmid: 16810739
references.citation: Eur J Immunol. 2006 Aug;36(8):2116-27
references.pmid: 16856206
references.citation: J Immunol. 2006 Nov 15;177(10):7322-31
references.pmid: 17082651
references.citation: Cell. 2007 Nov 30;131(5):994-1008
references.pmid: 18045540
references.citation: Hum Immunol. 2007 Dec;68(12):986-92
references.pmid: 18191727
references.citation: J Allergy Clin Immunol. 2009 Jan;123(1):67-73.e3
references.pmid: 19062085
references.citation: J Allergy Clin Immunol. 2009 Feb;123(2):472-8
references.pmid: 19064280
references.citation: Allergy. 2009 Jul;64(7):995-1002
references.pmid: 19630858
references.citation: J Immunol. 2009 Sep 15;183(6):3652-60
references.pmid: 19710468
references.citation: Nature. 2009 Oct 8;461(7265):819-22
references.pmid: 19783980
references.citation: Sci Signal. 2010;3(105):ra4
references.pmid: 20086239
references.citation: J Immunol. 2010 Apr 15;184(8):4568-74
references.pmid: 20237293
references.citation: Nature. 2010 Apr 29;464(7293):1362-6
references.pmid: 20200520
references.citation: Immunity. 2010 May 28;32(5):593-604
references.pmid: 20510870
references.citation: Blood. 2011 Mar 24;117(12):3421-9
references.pmid: 21233313
references.citation: Immunol Rev. 2011 Jul;242(1):144-60
references.pmid: 21682743
references.citation: Immunity. 2011 Jun 24;34(6):830-42
references.pmid: 21703538
references.citation: Allergy. 2011 Aug;66(8):1107-13
references.pmid: 21371044
references.citation: Nat Rev Immunol. 2011 Nov;11(11):750-61
references.pmid: 22025054
references.citation: Curr Protoc Immunol. 2012 Feb;Chapter 8:Unit 8.17.1-20
references.pmid: 22314834
references.citation: J Clin Invest. 2012 Mar;122(3):787-95
references.pmid: 22378047
references.citation: Nature. 2012 Apr 26;484(7395):465-72
references.pmid: 22538607
references.citation: Nat Med. 2012 May;18(5):716-25
references.pmid: 22561835
references.citation: J Allergy Clin Immunol. 2001 Mar;107(3):535-41
references.pmid: 11240957
references.citation: Science. 2012 Jul 27;337(6093):431-5
references.pmid: 22837519
references.citation: J Immunol Methods. 2012 Sep 28;383(1-2):21-9
references.pmid: 22245389
references.citation: Cell Rep. 2012 Sep 27;2(3):470-7
references.pmid: 22999934
references.citation: J Allergy Clin Immunol. 2012 Oct;130(4):845-52
references.pmid: 22939755
references.citation: Eur J Immunol. 2012 Oct;42(10):2544-50
references.pmid: 23042651
references.citation: Immunol Rev. 2012 Nov;250(1):277-302
references.pmid: 23046136
references.citation: Immunity. 2012 Dec 14;37(6):1116-29
references.pmid: 23200826
references.citation: Free Radic Biol Med. 2013 Jan;54:1-16
references.pmid: 23124025
references.citation: J Immunol. 2013 Feb 1;190(3):904-12
references.pmid: 23275605
references.citation: Nat Immunol. 2013 Apr;14(4):364-71
references.pmid: 23435120
references.citation: Immunity. 2013 Mar 21;38(3):570-80
references.pmid: 23434060
references.citation: Nat Rev Immunol. 2013 Aug;13(8):607-14
references.pmid: 23827958
references.citation: J Allergy Clin Immunol. 2013 Oct;132(4):789-801; quiz 788
references.pmid: 24075190
references.citation: Immunity. 2013 Nov 14;39(5):963-75
references.pmid: 24210352
references.citation: Immunity. 2013 Nov 14;39(5):976-85
references.pmid: 24210353
references.citation: J Exp Med. 2013 Nov 18;210(12):2583-95
references.pmid: 24166714
references.citation: Immunity. 2013 Dec 12;39(6):1158-70
references.pmid: 24332033
references.citation: J Leukoc Biol. 2014 Jan;95(1):161-8
references.pmid: 24018352
references.citation: Immunity. 2014 Feb 20;40(2):274-88
references.pmid: 24530056
references.citation: J Allergy Clin Immunol. 2014 Apr;133(4):952-60
references.pmid: 24084078
references.citation: Leukemia. 2014 Apr;28(4):951-4
references.pmid: 24369304
references.citation: J Invest Dermatol. 2014 May;134(5):1202-10
references.pmid: 24499736
references.citation: Nat Rev Immunol. 2014 Jun;14(6):392-404
references.pmid: 24854589
references.citation: Eur J Immunol. 2014 Oct;44(10):3045-55
references.pmid: 25070188
references.citation: Curr Opin Immunol. 2014 Dec;31:1-7
references.pmid: 25086241
references.citation: J Clin Invest. 2001 Jun;107(11):1357-64
references.pmid: 11390417
references.citation: J Allergy Clin Immunol. 2001 Aug;108(2):205-11
references.pmid: 11496235
references.citation: J Immunol. 2002 Jun 15;168(12):6199-207
references.pmid: 12055233