TY - JOUR
T1 - IFN-γ Drives human monocyte differentiation into highly proinflammatory macrophages that resemble a phenotype relevant to psoriasis
AU - Luque-Martin, Rosario
AU - Angell, Davina C.
AU - Kalxdorf, Mathias
AU - Bernard, Sharon
AU - Thompson, William
AU - Eberl, H. Christian
AU - Ashby, Charlotte
AU - Freudenberg, Johannes
AU - Sharp, Catriona
AU - van den Bossche, Jan
AU - de Jonge, Wouter J.
AU - Rioja, Inmaculada
AU - Prinjha, Rab K.
AU - Neele, Annette E.
AU - de Winther, Menno P. J.
AU - Mander, Palwinder K.
N1 - Funding Information:
This work was supported by the Fondation Leducq (Transatlantic Network Grant CVD-16 to M.P.J.d.W.), the Netherlands Heart Foundation (CVON 2011/B019, CVON 2017-20, and 2019B016 to M.P.J.d.W. and 2020T029 to A.E.N.), Amsterdam Cardiovascular Sciences (to J.V.d.B., A.E.N., and M.P.J.d.W.), the Netherlands Heart Foundation and Spark-Holding BV (2015B002 to M.P.J.d.W.), and the European Union's Horizon 2020 Research and Innovation Program under Grant ITN-2014-EID-641665 (ITN-grant EPIMAC to M.P.J.d.W.).
Funding Information:
This work was supported by the Fondation Leducq (Transatlantic Network Grant CVD-16 to M.P.J.d.W.), the Netherlands Heart Foundation (CVON 2011/B019, CVON 2017-20, and 2019B016 to M.P.J.d.W. and 2020T029 to A.E.N.), Amsterdam Cardiovascular Sciences (to J.V.d.B., A.E.N., and M.P.J.d.W.), the Netherlands Heart Foundation and Spark-Holding BV (2015B002 to M.P.J.d.W.), and the European Union’s Horizon 2020 Research and Innovation Program under Grant ITN-2014-EID-641665 (ITN-grant EPIMAC to M.P.J.d.W.).
Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - As key cells of the immune system, macrophages coordinate the activation and regulation of the immune response. Macrophages present a complex phenotype that can vary from homeostatic, proinflammatory, and profibrotic to anti-inflammatory phenotypes. The factors that drive the differentiation from monocyte to macrophage largely define the resultant phenotype, as has been shown by the differences found in M-CSF- and GM-CSF-derived macrophages. We explored alternative inflammatory mediators that could be used for in vitro differentiation of human monocytes into macrophages. IFN-g is a potent inflammatory mediator produced by lymphocytes in disease and infections. We used IFN-g to differentiate human monocytes into macrophages and characterized the cells at a functional and proteomic level. IFN-g alone was sufficient to generate macrophages (IFN-g Mf) that were phagocytic and responsive to polarization. We demonstrate that IFN-g Mf are potent activators of T lymphocytes that produce IL-17 and IFN-g. We identified potential markers (GBP-1, IP-10, IL-12p70, and IL-23) of IFN-g Mf and demonstrate that these markers are enriched in the skin of patients with inflamed psoriasis. Collectively, we show that IFN-g can drive human monocyte to macrophage differentiation, leading to bona fide macrophages with inflammatory characteristics.
AB - As key cells of the immune system, macrophages coordinate the activation and regulation of the immune response. Macrophages present a complex phenotype that can vary from homeostatic, proinflammatory, and profibrotic to anti-inflammatory phenotypes. The factors that drive the differentiation from monocyte to macrophage largely define the resultant phenotype, as has been shown by the differences found in M-CSF- and GM-CSF-derived macrophages. We explored alternative inflammatory mediators that could be used for in vitro differentiation of human monocytes into macrophages. IFN-g is a potent inflammatory mediator produced by lymphocytes in disease and infections. We used IFN-g to differentiate human monocytes into macrophages and characterized the cells at a functional and proteomic level. IFN-g alone was sufficient to generate macrophages (IFN-g Mf) that were phagocytic and responsive to polarization. We demonstrate that IFN-g Mf are potent activators of T lymphocytes that produce IL-17 and IFN-g. We identified potential markers (GBP-1, IP-10, IL-12p70, and IL-23) of IFN-g Mf and demonstrate that these markers are enriched in the skin of patients with inflamed psoriasis. Collectively, we show that IFN-g can drive human monocyte to macrophage differentiation, leading to bona fide macrophages with inflammatory characteristics.
UR - http://www.scopus.com/inward/record.url?scp=85111258760&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.2001310
DO - 10.4049/jimmunol.2001310
M3 - Article
C2 - 34233910
VL - 207
SP - 555
EP - 568
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -