Hypoxia-dependent regulation of inflammatory pathways in immune cells

Taylor, Cormac T.; Doherty, Glen; Fallon, Padraic G.; Cummins, Eoin P.

doi:10.1172/jci84433

Cited by 166 publications

(145 citation statements)

References 125 publications

(152 reference statements)

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“…1B and C). Present findings contrast with the general concept that HIFs are important regulators of inflammation and immune responses (21)(22)(23). For example, activation of neutrophils by HIFs is largely considered proinflammatory (23)(24)(25).…”

Section: Short-term Exposure To Intermittent Hypoxia Reshapes Circadicontrasting

confidence: 99%

Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease

Lee

Gulla

et al. 2020

Preprint

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Obstructive sleep apnea (OSA) results from intermittent episodes of airway collapse and hypoxia and is associated with a host of health complications including dementia, diabetes, heart failure, and stroke. Cellular mechanisms causing disease progression across multiple systems in OSA are unknown. Although it is known that pulmonary diseases share general mechanisms, such as systemic inflammation and oxidative stress, there is an incomplete understanding of the early-stage changes to the lung from OSA. Using intermittent hypoxia (IH) as a mouse model of OSA, we showed profound cell-type specific changes in genome-wide expression in the lung. With single-cell RNA analysis, we identified substantial similarities between lungs of mice exposed to IH and human lung tissue from patients with pulmonary disease--most notably pulmonary hypertension, COPD, and asthma. Many IH-responsive genes encode targets of drugs currently available to treat pulmonary disease. Present data provide insights into the initiation of specific cellular responses which drive disease progression in a model of OSA. This information can help direct therapies to the most relevant cells and molecular pathways.

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Section: Short-term Exposure To Intermittent Hypoxia Reshapes Circadicontrasting

confidence: 99%

Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease

Lee

Gulla

et al. 2020

Preprint

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“…HIF has cell type-specific roles, which have a profound impact on immune cell gene expression and downstream effector function. The specific functions of HIF in individual immune cell types has been recently reviewed and will be discussed only briefly here (reviewed in REFS 11,12). In neutrophils, HIF has a key role in the regulation of lifespan, antimicrobial peptide production and apoptosis 47,48 .…”

Section: Hif Modulation Of Immune Cell Functionmentioning

confidence: 99%

“…Alternatively, in mucosal immune cells, hypoxia can promote immune cell activity and survival through HIF activation. In summary, hypoxia has a complex role in inflammation, but notably, multiple studies have now demonstrated that the net effect of pharmacological HIF activation through hydroxylase inhibition is profoundly anti-inflammatory 11 .…”

Section: Hypoxia In Pathological Immune Nichesmentioning

confidence: 99%

“…In terms of inflammatory disease, a number of pre-clinical studies have now demonstrated that hydroxylase inhibitors are effective in reducing inflammation 11,134 (TABLE 1). This effectiveness has been demonstrated in models of IBD, renal transplant and renal ischaemia.…”

Section: Targeting the Hif Pathwaymentioning

confidence: 99%

“…Understanding the nature of immunological niches and how the niche microenvironment affects immune and inflammatory activity may allow the identification of new therapeutic targets for the control of inflammatory disease. One common feature of the immunological niche microenvironment that has a key role in immunity and inflammation in both health and disease is hypoxia, the condition that arises when cellular oxygen demand exceeds supply 11–13 (BOXES 1,2; FIGS 1,2). …”

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confidence: 99%

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Regulation of immunity and inflammation by hypoxia in immunological niches

2017

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Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

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Sensitive Activatable Nanoprobes for Real‐Time Ratiometric Magnetic Resonance Imaging of Reactive Oxygen Species and Ameliorating Inflammation In Vivo

Liu

et al. 2022

Advanced Materials

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Imaging‐guided real‐time monitoring of the treatment process of inflammatory diseases is important for the timely adjustment of treatment planning to lower unnecessary side effects and improve treatment outcomes. However, it is difficult to reflect the dynamic changes of inflammation in vivo with enough tissue penetration depth. Here a novel nanotheranostic agent (denominated TMSN@PM) with platelet membrane (PM)‐coated, tempol‐grafted, manganese‐doped, mesoporous silica nanoparticles is developed. The PM endows the TMSN@PM with the ability to target inflammation sites, which are verified by fluorescence imaging with Cyanine5 carboxylic acid (Cy5)‐labeled TMSN@PM. Under the inflammatory environment (mild acidity and excess reactive oxygen species (ROS)), TMSN@PM can scavenge the excess ROS, thereby alleviating inflammation, degrade, and release manganese ions for enhanced magnetic resonance imaging (MRI). The relaxation changes (ΔR1) are almost linearly correlated with the concentration of H2O2, which can reflect the degree of inflammation. This method offers a non‐invasive imaging‐based strategy for early prediction of the therapeutic outcomes in inflammatory therapy, which may contribute to precision medicine in terms of prognostic stratification and therapeutic planning in future.

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Hypoxia-dependent regulation of inflammatory pathways in immune cells

Cited by 166 publications

References 125 publications

Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease

Short-term exposure to intermittent hypoxia leads to changes in gene expression seen in chronic pulmonary disease

Regulation of immunity and inflammation by hypoxia in immunological niches

Sensitive Activatable Nanoprobes for Real‐Time Ratiometric Magnetic Resonance Imaging of Reactive Oxygen Species and Ameliorating Inflammation In Vivo

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