IL‐3 synergises with basophil‐derived IL‐4 and IL‐13 to promote the alternative activation of human monocytes

European Journal of Immunology - Tập 45 Số 7 - Trang 2042-2051 - 2015
Francesco Borriello1,2, Michele Longo2, Rosa Spinelli2, Antonio Pecoraro2, Francescopaolo Granata1,2, Rosaria Ilaria Staiano1,2, Stefania Loffredo1,2, Giuseppe Spadaro1,2, Francesco Béguinot1,2, John T. Schroeder3, Gianni Marone1,2
1Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy
2Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy
3Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, USA

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1038/nri3476

10.1126/science.1221064

10.1038/nature11047

10.1016/j.immuni.2013.10.006

10.1016/j.immuni.2013.10.005

10.1016/j.coi.2014.07.004

10.1002/eji.201142318

10.1111/j.1600-065X.2011.01023.x

10.1111/j.1398-9995.2011.02570.x

10.1067/mai.2001.117175

10.4049/jimmunol.177.10.7322

10.4049/jimmunol.172.12.7734

10.1038/jid.2014.16

10.1016/j.jaci.2013.07.046

10.1016/j.immuni.2012.11.014

10.1084/jem.20130761

10.1002/eji.201444731

10.1172/JCI59643

10.1016/j.immuni.2014.01.006

10.1016/j.immuni.2010.05.007

10.1016/j.jaci.2008.09.049

10.4049/jimmunol.0901342

10.1111/j.1398-9995.2009.02095.x

10.1111/j.0105-2896.2004.00215.x

10.1172/JCI7613

10.1111/j.1346-8138.2003.tb00329.x

10.1002/eji.200535564

10.1067/mai.2001.113237

Schroeder J. T., 1994, IgE‐dependent IL‐4 secretion by human basophils. The relationship between cytokine production and histamine release in mixed leukocyte cultures, J. Immunol., 153, 1808, 10.4049/jimmunol.153.4.1808

10.1111/j.1600-065X.2012.01164.x

10.1006/cyto.1997.0324

10.1182/blood-2009-11-255232

10.1016/j.freeradbiomed.2012.10.553

10.1002/eji.200635972

10.1016/j.humimm.2007.10.012

10.1016/j.immuni.2011.06.002

10.1016/j.jaci.2013.08.006

10.4049/jimmunol.0900864

10.1189/jlb.0313168

10.1016/1043-4666(94)90065-5

10.1006/cyto.1996.0064

10.4049/jimmunol.168.12.6199

10.1084/jem.179.4.1109

10.1038/nri3671

10.1016/j.jaci.2012.07.010

10.1038/ni.2541

10.1126/scisignal.2000567

10.4049/jimmunol.1201808

10.1038/nri3088

10.1038/nature08448

10.1016/j.celrep.2012.08.016

10.1038/leu.2013.385

10.1016/j.immuni.2012.08.025

10.1016/j.cell.2007.09.047

10.1038/nature08901

10.1016/j.immuni.2013.09.016

10.1016/j.jaci.2008.10.022

10.1038/nm.2678

10.1016/j.jim.2011.12.007

Schulz K. R., 2012, Single‐cell phospho‐protein analysis by flow cytometry, Curr. Protoc. Immunol., 8, 20

Thông tin
Thông tin xuất bản

European Journal of Immunology

Tập 45 Số 7

2042-2051

Thông tin tác giả