Interferon regulatory factor 8 governs myeloid cell development

Xia, Xueli; Wang, Wenxin; Yin, Kai; Wang, Shengjun

doi:10.1016/j.cytogfr.2020.03.003

Cited by 18 publications

(9 citation statements)

References 118 publications

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“…In vivo IRF-8 overexpression specifically attenuated MDSCs expansion and enhanced antitumor efficacy via the STAT3 and STAT5 signaling pathways [ 71 , 72 ]. Notably, IRF-8 promotes monocyte and dendritic cell differentiation but limits granulocyte development [ 73 ]. A recent study demonstrated that IRF8 overexpression in vivo selectively led to GPs proliferation and PMN-MDSCs expansion without appreciable expansion of MPs and M-MDSCs [ 71 ].…”

Section: Expansion and Activation Of Mdscsmentioning

confidence: 99%

Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy

Niu

et al. 2022

Mol Cancer

196

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The clinical responses observed following treatment with immune checkpoint inhibitors (ICIs) support immunotherapy as a potential anticancer treatment. However, a large proportion of patients cannot benefit from it due to resistance or relapse, which is most likely attributable to the multiple immunosuppressive cells in the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs), a heterogeneous array of pathologically activated immature cells, are a chief component of immunosuppressive networks. These cells potently suppress T-cell activity and thus contribute to the immune escape of malignant tumors. New findings indicate that targeting MDSCs might be an alternative and promising target for immunotherapy, reshaping the immunosuppressive microenvironment and enhancing the efficacy of cancer immunotherapy. In this review, we focus primarily on the classification and inhibitory function of MDSCs and the crosstalk between MDSCs and other myeloid cells. We also briefly summarize the latest approaches to therapies targeting MDSCs.

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Section: Expansion and Activation Of Mdscsmentioning

confidence: 99%

Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy

Niu

et al. 2022

Mol Cancer

196

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“…In myeloid cells, IRF8 expression is known to vary depending on the specific cell subset, stage of differentiation, and inflammatory setting 161 . Among the stimuli known to upregulate IRF8 expression, exposure to IFNγ induces the expression of IRF8 in a STAT1‐dependent manner 157 .…”

Section: The Transcriptional Machinery Of Abcsmentioning

confidence: 99%

“…In contrast to IRF5, IRF8 is also well-recognized for its crucial role in adaptive immune responses and, together with IRF4, is an important regulator of B cell differentiation [158][159][160]. IRF8 plays a redundant role with IRF4 in the early stages of B cell development, but only IRF8 is expressed in GC B cells where it helps establish their gene expression program and antagonize PC differentiation by cooperating with the Ets protein PU.1.In myeloid cells, IRF8 expression is known to vary depending on the specific cell subset, stage of differentiation, and inflammatory setting 161. Among the stimuli known to upregulate IRF8 expression, exposure to IFNγ induces the expression of IRF8 in a STAT1dependent manner 157.…”

mentioning

confidence: 99%

Molecular mechanisms controlling age‐associated B cells in autoimmunity*

Phalke

Rivera-Correa

Jenkins

et al. 2022

Immunological Reviews

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Age-associated B cells (ABCs) have emerged as critical components of immune responses. Their inappropriate expansion and differentiation have increasingly been linked to the pathogenesis of autoimmune disorders, aging-associated diseases, and infections. ABCs exhibit a distinctive phenotype and, in addition to classical B cell markers, often express the transcription factor T-bet and myeloid markers like CD11c; hence, these cells are also commonly known as CD11c + T-bet + B cells. Formation of ABCs is promoted by distinctive combinations of innate and adaptive signals. In addition to producing antibodies, these cells display antigen-presenting and proinflammatory capabilities. It is becoming increasingly appreciated that the ABC compartment exhibits a high degree of heterogeneity, plasticity, and sex-specific regulation and that ABCs can differentiate into effector progeny via several routes particularly in autoimmune settings. In this review, we will discuss the initial insights that have been obtained on the molecular machinery that controls ABCs and we will highlight some of the unique aspects of this control system that may enable ABCs to fulfill their distinctive role in immune responses. Given the expanding array of autoimmune disorders and pathophysiological settings in which ABCs are being implicated, a deeper understanding of this machinery could have important and broad therapeutic implications for the successful, albeit daunting, task of targeting these cells.

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“…In view of their important roles in the physiology of inflammation as well as in the execution of the corresponding functions by MDSCs, it is necessary to measure the expression levels of S100A8 and S100A9 40,41 . IRF8 (IFN regulatory factor 8), as reported in previous studies, 42–44 negatively regulates the development of MDSCs and other myeloid cells. Evaluating the expression of S100A8, S100A9, and IRF8 could help to precisely identify the presence of MDSCs in terms of biologic function.…”

Section: Resultsmentioning

confidence: 99%

Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma

Liu

Xing

et al. 2021

Journal of Leukocyte Biology

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Elimination of the posttraumatic inflammatory response and recovery of homeostasis are crucial for the positive prognosis of trauma patients. Myeloid‐derived suppressor cells (MDSCs) are known to play a regulatory role in the posttraumatic immune response in mice, but their induction source and involved potential mechanism are poorly understood. Here, we report that polymorphonuclear MDSCs (PMN‐MDSCs) are activated after trauma and are closely associated with the progression of the posttraumatic inflammatory response. In humans, lectin‐type oxidized LDL receptor 1 (LOX1) was used to specifically characterize LOX1+ PMN‐MDSCs. Trauma patients showed high intracellular reactive oxygen species (ROS) production, as well as activation of LOX1+ PMN‐MDSCs. These MDSCs contribute to the anti‐inflammatory immune response by regulating the Treg/Th17 and Th2/Th1 balances after trauma, increasing the levels of anti‐inflammatory factors, and decreasing the levels of proinflammatory factors. The number of LOX1+ PMN‐MDSCs was positively correlated with the positive clinical prognosis of trauma patients with infection. Activation of LOX1+ PMN‐MDSCs is mediated by NF‐κB signal, and TGF‐β1 may be as an important inducer for LOX1+ PMN‐MDSCs in the posttraumatic cytokine environment. In a pseudofracture trauma mouse model, we also observed the activation of PMN‐MDSCs, accompanying high levels of intracellular ROS production, NF‐κB phosphorylation, and changes in the inflammatory environment, in particularly by regulating the Treg/Th17 and Th2/Th1 balance. And more significantly, posttraumatic inflammation was alleviated in mice after transferring trauma‐derived PMN‐MDSCs, but aggravated after injecting with Gr1 agonistic antibody. These findings provide evidence for the specific role of PMN‐MDSCs in the regulation of posttraumatic inflammation.

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Interferon regulatory factor 8 governs myeloid cell development

Cited by 18 publications

References 118 publications

Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy

Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy

Molecular mechanisms controlling age‐associated B cells in autoimmunity*

Polymorphonuclear myeloid-derived suppressor cells link inflammation and damage response after trauma

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