TY - JOUR
T1 - IFN-y Drives Human Monocyte Differentiation into Highly Proinflammatory Macrophages That Resemble a Phenotype Relevant to Psoriasis
AU - Luque-Martin, Rosario
AU - Angell, Davina
AU - Kalxdorf, Mathias
AU - Bernard, Sharon
AU - Mohamed, Alhaleem
AU - Christian Eberl, H
AU - Ashby, Charlotte
AU - Freudenberg, Johannes
AU - Sharp, Catriona
AU - Van den Bossche, Jan
AU - J. de Jonge, Wouter
AU - Rioja, Inmaculada
AU - Prinjha, Rab
AU - Neele, Annette
AU - P.J. de Winther, Menno
AU - Mander, Palwinder
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-γ is a potent inflammatory mediator produced by lymphocytes in disease and infections. We used IFN-γ to differentiate human monocytes into macrophages and characterized the cells at a functional and proteomic level. IFN-γ alone was sufficient to generate macrophages (IFN-γ Mϕ) that were phagocytic and responsive to polarization. We demonstrate that IFN-γ Mϕ are potent activators of T lymphocytes that produce IL-17 and IFN-γ. We identified potential markers (GBP-1, IP-10, IL-12p70, and IL-23) of IFN-γ Mϕ and demonstrate that these markers are enriched in the skin of patients with inflamed psoriasis. Collectively, we show that IFN-γ 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-γ is a potent inflammatory mediator produced by lymphocytes in disease and infections. We used IFN-γ to differentiate human monocytes into macrophages and characterized the cells at a functional and proteomic level. IFN-γ alone was sufficient to generate macrophages (IFN-γ Mϕ) that were phagocytic and responsive to polarization. We demonstrate that IFN-γ Mϕ are potent activators of T lymphocytes that produce IL-17 and IFN-γ. We identified potential markers (GBP-1, IP-10, IL-12p70, and IL-23) of IFN-γ Mϕ and demonstrate that these markers are enriched in the skin of patients with inflamed psoriasis. Collectively, we show that IFN-γ can drive human monocyte to macrophage differentiation, leading to bona fide macrophages with inflammatory characteristics.
UR - https://journals.aai.org/jimmunol/article/207/2/555/234722/IFN-Drives-Human-Monocyte-Differentiation-into
U2 - 10.4049/jimmunol.2001310
DO - 10.4049/jimmunol.2001310
M3 - Article
SN - 0022-1767
VL - 207
SP - 555
EP - 568
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
M1 - 1550-6606
ER -