Purpose of review: Interferon-gamma (IFN-γ) is a pro-inflammatory cytokine that participates in the regulation of hematopoietic stem cells (HSC) during development and under homeostatic conditions. IFN-γ also plays a key pathogenic role in several diseases that affect hematopoiesis including aplastic anemia, hemophagocytic lymphohistiocytosis, and cirrhosis of the liver.
Recent findings: Studies have shown that increased IFN-γ negatively affects HSC homeostasis, skewing HSC towards differentiation over self-renewal and eventually causing exhaustion of the HSC compartment.
Summary: Here, we explore the mechanisms by which IFN-γ regulates HSC in both normal and pathological conditions. We focus on the role of IFN-γ signaling in HSC fate decisions, and the transcriptional changes it elicits. Elucidating the mechanisms through which IFN-γ regulates HSCs may lead to new therapeutic options to prevent or treat adverse hematologic effects of the many diseases to which IFN-γ contributes.
Keywords: Bone marrow; Bone marrow failure; Emergency hematopoiesis; Hematopoietic stem cells; Interferon-gamma; Terminal differentiation.