title: Impact of interferon-γ on hematopoiesis.
abstract: The proinflammatory cytokine interferon-γ (IFN-γ) is well known for its important role in innate and adaptive immunity against intracellular infections and for tumor control. Yet, it has become clear that IFN-γ also has a strong impact on bone marrow (BM) output during inflammation, as it affects the differentiation of most hematopoietic progenitor cells. Here, we review the impact of IFN-γ on hematopoiesis, including the function of hematopoietic stem cells (HSCs) and more downstream progenitors. We discuss which hematopoietic lineages are functionally modulated by IFN-γ and through which underlying molecular mechanism(s). We propose the novel concept that IFN-γ acts through upregulation of suppressor of cytokine signaling molecules, which impairs signaling of several cytokine receptors. IFN-γ has also gained clinical interest from different angles, and we discuss how chronic IFN-γ production can lead to the development of anemia and BM failure and how it is involved in malignant hematopoiesis. Overall, this review illustrates the wide-ranging effect of IFN-γ on the (patho-)physiological processes in the BM.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: de Bruin
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Carlijn
authors.initials: C
authors.lastname: Voermans
authors.affiliation: Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Nolte
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D016207:Cytokines; D014157:Transcription Factors; D007371:Interferon-gamma