IFN-y Drives Human Monocyte Differentiation into Highly Proinflammatory Macrophages That Resemble a Phenotype Relevant to Psoriasis

Rosario Luque-Martin, Davina Angell, Mathias Kalxdorf, Sharon Bernard, Alhaleem Mohamed, H Christian Eberl, Charlotte Ashby, Johannes Freudenberg, Catriona Sharp, Jan Van den Bossche, Wouter J. de Jonge, Inmaculada Rioja, Rab Prinjha, Annette Neele, Menno P.J. de Winther, Palwinder Mander

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number1550-6606
Pages (from-to)555-568
Number of pages13
JournalJournal of Immunology
Volume207
Issue number2
DOIs
Publication statusPublished - 15 Jul 2021

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