Regulation of humoral immune response by HIF-1α-dependent metabolic reprogramming of the germinal center reaction

Li, Lingyun; Feng, Chunlei; Qin, Jun; Li, Dali; Liu, Mingyao; Han, Shuhua; Zheng, Biao

doi:10.1016/j.cellimm.2021.104409

Cited by 19 publications

(17 citation statements)

References 61 publications

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“…While there are issues pertaining to the duration and level of HIF stabilization, the data strongly suggest that hypoxia influences B cell function among at least the GC subset that is hypoxic (~80% of those quantified in spleens). This model is supported by new work providing evidence that Cγ1-Cre- and Cd21 -Cre-driven deletion of Hif1a decreased GC and anti-NP antibody responses [ 228 ]. Nevertheless, further studies and elucidation of the mechanisms that operate after HIF-1, HIF-2, or both are selectively inactivated within GC B cells are needed.…”

Section: Decisions Decisions—b Cells After Activationmentioning

confidence: 78%

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

et al. 2021

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The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody (Ab) secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against infection. With this backdrop, it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise, persist, and meet the challenge of secreting vast amounts of these glycoproteins. Whereas plasmablasts and plasma cells (PCs) are the primary sources of secreted Abs, the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential fates. At each step, cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for nutrients. Nutrients in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription, translation, and metabolism. This review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab secretion. Salient findings of this group and others, sometimes exhibiting differences, will be summarized with regard to the journey to a distinctive metabolic program in PCs.

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Section: Decisions Decisions—b Cells After Activationmentioning

confidence: 78%

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

et al. 2021

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“…HIF-1α was shown to be dynamically regulated in GC B cells to ensure the different functions of HIF-1α at different stages ( 67 ). B cells in dark zones differentiate into centroblasts accompanied by BCL-6 upregulation and cMyc inhibition, and HIF-1α-mediated glycolytic activity under normoxia (aerobic glycolysis) provides energy for rapid proliferation of centroblasts ( 84 ). B cells then enter into the GC light zone and differentiation into centrocytes.…”

Section: Hypoxic Regulation Of B Cell Biologymentioning

confidence: 99%

Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells

Zhang

et al. 2022

Front. Immunol.

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Hypoxia is a common hallmark of healthy tissues in physiological states or chronically inflamed tissues in pathological states. Mammalian cells sense and adapt to hypoxia mainly through hypoxia-inducible factor (HIF) signaling. Many studies have shown that hypoxia and HIF signaling play an important regulatory role in development and function of innate immune cells and T cells, but their role in B cell biology is still controversial. B cells experience a complex life cycle (including hematopoietic stem cells, pro-B cells, pre-B cells, immature B cells, mature naïve B cells, activated B cells, plasma cells, and memory B cells), and the partial pressure of oxygen (PO2) in the corresponding developmental niche of stage-specific B cells is highly dynamic, which suggests that hypoxia and HIF signaling may play an indispensable role in B cell biology. Based on the fact that hypoxia niches exist in the B cell life cycle, this review focuses on recent discoveries about how hypoxia and HIF signaling regulate the development, metabolism, and function of B cells, to facilitate a deep understanding of the role of hypoxia in B cell-mediated adaptive immunity and to provide novel strategies for vaccine adjuvant research and the treatment of immunity-related or infectious diseases.

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“…Hypoxia can lead to malignant progression of tumor cells through the following mechanisms: inhibiting the activity of immune cells, providing energy support for tumor cells, improving immune resistance of tumor cells, inhibiting apoptosis of tumor cells, and promoting metastasis of tumor cells ( 118 , 119 ). ERRα cooperates with HIF-1α to regulate angiogenesis and glycolysis, thus promoting the growth of tumor cells under hypoxia, while stable HIF-1α further increases the expression of ERRα at the transcriptional level ( 77 ).…”

Section: The Involvement Of Pyroptosis In Endometrial Carcinomamentioning

confidence: 99%

Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis

Mao

et al. 2022

Front. Oncol.

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Oxygen is critical to energy metabolism, and tumors are often characterized by a hypoxic microenvironment. Owing to the high metabolic energy demand of malignant tumor cells, their survival is promoted by metabolic reprogramming in the hypoxic microenvironment, which can confer tumor cell resistance to pyroptosis. Pyroptosis resistance can inhibit anti-tumor immunity and promote the development of malignant tumors. Hypoxia inducible factor-1α (HIF-1α) is a key regulator of metabolic reprogramming in tumor cells, and estrogen-related receptor α (ERRα) plays a key role in regulating cellular energy metabolism. Therefore, the close interaction between HIF-1α and ERRα influences the metabolic and functional changes in cancer cells. In this review, we summarize the reprogramming of tumor metabolism involving HIF-1α/ERRα. We review our understanding of the role of HIF-1α/ERRα in promoting tumor growth adaptation and pyroptosis resistance, emphasize its key role in energy homeostasis, and explore the regulation of HIF-1α/ERRα in preventing and/or treating endometrial carcinoma patients. This review provides a new perspective for the study of the molecular mechanisms of metabolic changes in tumor progression.

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Regulation of humoral immune response by HIF-1α-dependent metabolic reprogramming of the germinal center reaction

Cited by 19 publications

References 61 publications

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

Supplying the trip to antibody production—nutrients, signaling, and the programming of cellular metabolism in the mature B lineage

Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells

Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis

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