Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease

Meng, Xianjun; Grötsch, Bettina; Luo, Yubin; Knaup, Karl X.; Wiesener, Michael S.; Chen, Xiaoxiang; Jantsch, Jonathan; Fillatreau, Simon; Schett, Georg; Bözec, Aline

doi:10.1038/s41467-017-02683-x

Cited by 198 publications

(183 citation statements)

References 57 publications

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“…Indeed, B‐cell hypoxia in germinal centers leads to a decreased proliferation and altered immunoglobulin class switching of B cells . The use of HIF1α‐deficient chimeric mice confirms the important role for HIF1α in the development of B cells and autoimmunity , and recently, a critical role for HIF1α in B cells for IL‐10 production has been identified .…”

Section: Crosstalk Between Hif and Sepsismentioning

confidence: 64%

Hypoxia‐inducible factors in metabolic reprogramming during sepsis

2020

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Sepsis is a highly heterogeneous syndrome that is caused by an imbalanced host response to infection. Despite huge investments, sepsis remains a contemporary threat with significant burden on health systems. Vascular dysfunction and elevated oxygen consumption by highly metabolically active immune cells result in tissue hypoxia during inflammation. The transcription factor hypoxia-inducible factor-1a (HIF1a), and its family members, plays an important role in cellular metabolism and adaptation to cellular stress caused by hypoxia. In this review, we discuss the role of HIF in sepsis. We show possible mechanisms by which the inflammatory response activated during sepsis affects the HIF pathway. The activated HIF pathway in turn changes the metabolism of both innate and adaptive immune cells. As HIF expression in leukocytes of septic patients can be directly linked with mortality, we discuss multiple ways of interfering with the HIF signaling pathway.

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Section: Crosstalk Between Hif and Sepsismentioning

confidence: 64%

Hypoxia‐inducible factors in metabolic reprogramming during sepsis

2020

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“…A very interesting point is that these adaptations in the BM due to loss of HIF1α appear to impact on B1 B cells and autoimmunity [57]. In accordance, recent elegant experiments have revealed that HIF1α is important for expansion of CD1d high CD5 + B cells via glycolysis and production of anti-inflammatory IL-10 by those B cells [58]. Further studies performed under hypoxic conditions are required to fully explore the physiological role of glycolysis and OxPhos in pro-B and pre-B cells.…”

Section: Oxidative Phosphorylation and Glycolysis In Pro- And Pre-mentioning

confidence: 96%

Regulation of Energy Metabolism during Early B Lymphocyte Development

Urbanczyk

Stein

Schuh

et al. 2018

IJMS

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The most important feature of humoral immunity is the adaptation of the diversity of newly generated B cell receptors, that is, the antigen receptor repertoire, to the body’s own and foreign structures. This includes the transient propagation of B progenitor cells and B cells, which possess receptors that are positively selected via anabolic signalling pathways under highly competitive conditions. The metabolic regulation of early B-cell development thus has important consequences for the expansion of normal or malignant pre-B cell clones. In addition, cellular senescence programs based on the expression of B cell identity factors, such as Pax5, act to prevent excessive proliferation and cellular deviation. Here, we review the basic mechanisms underlying the regulation of glycolysis and oxidative phosphorylation during early B cell development in bone marrow. We focus on the regulation of glycolysis and mitochondrial oxidative phosphorylation at the transition from non-transformed pro- to pre-B cells and discuss some ongoing issues. We introduce Swiprosin-2/EFhd1 as a potential regulator of glycolysis in pro-B cells that has also been linked to Ca2+-mediated mitoflashes. Mitoflashes are bioenergetic mitochondrial events that control mitochondrial metabolism and signalling in both healthy and disease states. We discuss how Ca2+ fluctuations in pro- and pre-B cells may translate into mitoflashes in early B cells and speculate about the consequences of these changes.

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“…HIF expression, like that of inflammatory cytokines, can be triggered through pathways dependent and independent of oxygen, aggravating the disease [55][56][57][58]. Indeed, the number of HIF-1αpositive cells is directly related to the extent of infiltration by inflammatory endothelial cells and to the severity of synovitis [59,60]. Excessive production of reactive oxygen species (ROS) causes the breakdown of proteoglycans, hyaluronic acid, chondroitin sulfate, and collagen [61], which destroys the joints.…”

Section: Discussionmentioning

confidence: 99%

Potential mechanisms of action of celastrol against rheumatoid arthritis: transcriptomic and proteomic analysis

Song

Dai

Zhang

et al. 2020

Preprint

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Background:The natural triterpene celastrol exhibits potential anti-inflammatory activity in inflammatory diseases such as rheumatoid arthritis (RA). Methods:Here we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, labelfree relatively quantitative proteomics and molecular docking.Results: Expression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. Conclusions:These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

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Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease

Cited by 198 publications

References 57 publications

Hypoxia‐inducible factors in metabolic reprogramming during sepsis

Hypoxia‐inducible factors in metabolic reprogramming during sepsis

Regulation of Energy Metabolism during Early B Lymphocyte Development

Potential mechanisms of action of celastrol against rheumatoid arthritis: transcriptomic and proteomic analysis

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