The PRO-inflammatory cytokine interleukin-1 is a key regulator of hematopoietic Stem cell fate and function

Pietras, Eric M.; Mirantes-Barbeito, Cristina; Fong, Sarah; Loeffler, Dirk; Kovtonyuk, Larisa V.; Zhang, Siyi; Lakshminarasimhan, Ranjani; Chin, Chih Peng; Techner, Jose-Marc; Will, Britta; Nerlov, Claus; Steidl, Ulrich; Manz, Markus G.; Schroeder, Timm; Passegué, Emmanuelle

doi:10.1016/j.exphem.2016.06.066

Cited by 6 publications

(7 citation statements)

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“…Indeed, it has been observed that administration of IL-1 prior lethal doses of radiation protects mice from fatal hematopoietic syndrome (113), which is associated to the role of IL-1 on cell cycle activation through the expansion of HSPCs and myeloid precursor cells (114)(115)(116). Moreover, chronic IL-1 exposure leads to impairment of HSCs function (117). However, the mechanisms leading to these effects are still largely unknown.…”

Section: Interleukin-1 and -6 And Their Role In Hematopoiesismentioning

confidence: 99%

The role of inflammation in hematopoiesis and bone marrow failure: What can we learn from mouse models?

2022

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Hematopoiesis is a remarkable system that plays an important role in not only immune cell function, but also in nutrient transport, hemostasis and wound healing among other functions. Under inflammatory conditions, steady-state hematopoiesis switches to emergency myelopoiesis to give rise to the effector cell types necessary to fight the acute insult. Sustained or aberrant exposure to inflammatory signals has detrimental effects on the hematopoietic system, leading to increased proliferation, DNA damage, different forms of cell death (i.e., apoptosis, pyroptosis and necroptosis) and bone marrow microenvironment modifications. Together, all these changes can cause premature loss of hematopoiesis function. Especially in individuals with inherited bone marrow failure syndromes or immune-mediated aplastic anemia, chronic inflammatory signals may thus aggravate cytopenias and accelerate disease progression. However, the understanding of the inflammation roles in bone marrow failure remains limited. In this review, we summarize the different mechanisms found in mouse models regarding to inflammatory bone marrow failure and discuss implications for future research and clinical practice.

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Section: Interleukin-1 and -6 And Their Role In Hematopoiesismentioning

confidence: 99%

The role of inflammation in hematopoiesis and bone marrow failure: What can we learn from mouse models?

2022

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“…For example, macrophage (M)-CSF deficiency reduced atherosclerotic lesion size in both diet-induced hypercholesteremia and Apoe -/atherosclerotic mouse models (26,27). In addition to atherosclerosis, following a myocardial infarction, sympathetic activity initiates extramedullary haematopoiesis via the canonical inflammatory cytokine interleukin (IL)-1β, which drives HSCs toward myelopoiesis (35)(36)(37). Finally, we have recently shown that…”

Section: Cytokines Influence Myeloid Cells To Proliferate and Differementioning

confidence: 99%

Hematopoiesis is regulated by cholesterol efflux pathways and lipid rafts: connections with cardiovascular diseases

Morgan¹,

Fang²,

Lancaster³

et al. 2020

Journal of Lipid Research

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Lipid rafts are highly ordered regions of the plasma membrane that are enriched in cholesterol and sphingolipids and play important roles in many cells. In hematopoietic stem and progenitor cells (HSPCs), lipid rafts house receptors critical for normal hematopoiesis. Lipid rafts also can bind and sequester kinases that induce negative feedback pathways to limit proliferative cytokine receptor cycling back to the cell membrane. Modulation of lipid rafts occurs through an array of mechanisms, with optimal cholesterol efflux one of the major regulators. As such, cholesterol homeostasis also regulates hematopoiesis. Increased lipid raft content, which occurs in response to changes in cholesterol efflux in the membrane, can result in prolonged receptor occupancy in the cell membrane and enhanced signaling. In addition, certain diseases, like diabetes, may contribute to lipid raft formation and affect cholesterol retention in rafts. In this review, we explore the role of lipid raft-related mechanisms in hematopoiesis and CVD (specifically, atherosclerosis) and discuss how defective cholesterol efflux pathways in HSPCs contribute to expansion of lipid rafts, thereby promoting myelopoiesis and thrombopoiesis. We also discuss the utility of cholesterol acceptors in contributing to lipid raft regulation and disruption, and highlight the potential to manipulate these pathways for therapeutic gain in CVD as well as other disorders with aberrant hematopoiesis.

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“…1,2 Several cytokines, including interferon alpha (IFNa), interferon gamma (IFNg) and interleukin-1beta (IL1b) all have been shown to drive quiescent hematopoietic stem cells (HSCs) into cycle and alter hematopoietic output. [3][4][5][6] Acute exposure to type I interferons (IFN-1), which includes IFNa and interferon beta (IFNb), promotes HSC proliferation and emergency megakaryopoiesis. 3,7 Likewise, IL1b exposure induces transient HSC proliferation and myelopoiesis.…”

Section: Introductionmentioning

confidence: 99%

“…3,7 Likewise, IL1b exposure induces transient HSC proliferation and myelopoiesis. 5,8 These changes enhance blood production and immune function under conditions of stress. Inflammatory cytokines also help maintain basal hematopoietic output.…”

Section: Introductionmentioning

confidence: 99%

Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis

Yang

Wang

et al. 2022

Preprint

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Type I interferon (IFN-1) regulates gene expression and hematopoiesis both during development and in response to inflammatory stress. We previously showed that during development, hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) induce IFN-1 target genes shortly before birth in mice. This coincides with the onset of a transition to adult hematopoiesis, and it drives expression of genes associated with antigen presentation. However, it is not clear whether perinatal IFN-1 modulates hematopoietic output, as has been observed in contexts of inflammation. We have characterized hematopoiesis at several different stages of blood formation, from HSCs to mature blood cells, and found that loss of the IFN-1 receptor (IFNAR1) leads to depletion of several phenotypic HSC and MPP subpopulations in neonatal and juvenile mice. Committed lymphoid and myeloid progenitor populations simultaneously expand. These changes had surprisingly little effect on production of more differentiated blood cells. Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) resolved the discrepancy between the extensive changes in progenitor numbers and modest changes in hematopoiesis, revealing stability in most MPP populations in Ifnar1-deficient neonates when the populations were identified based on gene expression rather than surface marker phenotype. Thus, basal IFN-1 signaling has only modest effects on hematopoiesis. Discordance between transcriptionally- and phenotypically-defined MPP populations may impact interpretations of how IFN-1 shapes hematopoiesis in other contexts, such as aging or inflammation.KEY POINTSLoss of type I Interferon signaling in neonatal mice depletes immature blood progenitors without compromising postnatal hematopoiesisProgenitor populations remain intact when measured by single cell transcriptomes rather than surface marker phenotypes

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The PRO-inflammatory cytokine interleukin-1 is a key regulator of hematopoietic Stem cell fate and function

Cited by 6 publications

References 0 publications

The role of inflammation in hematopoiesis and bone marrow failure: What can we learn from mouse models?

The role of inflammation in hematopoiesis and bone marrow failure: What can we learn from mouse models?

Hematopoiesis is regulated by cholesterol efflux pathways and lipid rafts: connections with cardiovascular diseases

Basal type I interferon signaling has only modest effects on neonatal and juvenile hematopoiesis

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