A PHD in immunosuppression: oxygen-sensing pathways regulate immunosuppressive Tregs

Zou, Weiping; Shah, Yatrik M.

doi:10.1172/jci130009

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…Tissue hypoxia occurs following tissue injury, infection, inflammation, and rapid tumor growth. Residents or recruited immune cells need to adapt rapidly to a hypoxic environment [58] . Hypoxia in solid tumors promotes the secretion of chemokines and activation of their receptors.…”

Section: Discussionmentioning

confidence: 99%

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Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity

et al. 2022

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The role of regulatory T cells (Tregs), damage-associated molecular patterns (DAMPs), and myeloid-derived suppressor cells (MDSCs) in the mechanism of innate and adaptive immune responses in chronic obstructive pulmonary disease (COPD) is not well understood. Evaluating the presence of Tregs in the bronchoalveolar lavage fluid (BALF) and peripheral blood in patients with COPD, and assessment of the relationship between Tregs, MDSCs, and DAMPs as factors activating innate and adaptive immune responses. Description of the association between immune and clinical parameters in COPD. Thirty-one patients with COPD were enrolled. Clinical parameters (forced expiratory volume in one second [FEV1], forced vital capacity, total lung capacity [TLC], diffusion capacity of carbon monoxide, and B-BMI, O-obstruction, D-dyspnea, E-exercise [BODE]) were assessed. Tregs and MDSCs were investigated in the BALF and blood using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. The levels of defensin (DEF2), galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), heat shock protein-27 (HSP27), and surfactant protein A were assessed via sandwich enzyme-linked immunosorbent assay. The percentage of Tregs was significantly higher in the blood than in the BALF, in contrast to the mean fluorescence intensity of forkhead box P3 (FoxP3). Significant associations were observed between Tregs and HSP27 (r = 0.39), Gal-1 (r = 0.55), Gal-9 (r = −0.46), and MDSCs (r = −0.50), and between FoxP3 and Gal-1 (r = −0.42), Gal-3 (r = −0.39), and MDSCs (r = −0.43). Tregs and clinical parameters, including FEV1%pred (r = 0.39), residual volume (RV)%pred (r = −0.56), TLC%pred (r = −0.55), RV/TLC (r = −0.50), arterial oxygen saturation (r = −0.38), and arterial oxygen pressure (r = −0.39) were significantly correlated. FoxP3 was significantly interlinked with RV/TLC (r = −0.52), arterial oxygen pressure (r = 0.42), and BODE index (r = −0.57). The interaction between innate and adaptive immune responses in patients with COPD was confirmed. The expression of Tregs in BALF may have prognostic value in patients with COPD. The conversion of immune responses to clinical parameters appears to be associated with disease severity.

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Section: Discussionmentioning

confidence: 99%

“…Residents or recruited immune cells need to adapt rapidly to a hypoxic environment. [ 58 ] Hypoxia in solid tumors promotes the secretion of chemokines and activation of their receptors. This may promote the mobilization of various cell types in the body and the recruitment of Tregs to tumor sites.…”

Section: Discussionmentioning

confidence: 99%

Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity

et al. 2022

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“…The expression of Treg cells is closely related to the pathological state of the respiratory tract, and its functional impairment can potentially lead to autoimmune diseases. The increase of HIF‐1α and HIF‐2α in hypoxic conditions can inhibit the differentiation of Treg cells 181 . The downregulation of prolyl hydroxylase domain under hypoxic conditions can increase HIF‐2α levels and lead to impaired Treg cell function, but does not affect the expression of Foxp3 181 .…”

Section: Effect Of Hypoxia On Immune Cellsmentioning

confidence: 99%

“…The increase of HIF‐1α and HIF‐2α in hypoxic conditions can inhibit the differentiation of Treg cells 181 . The downregulation of prolyl hydroxylase domain under hypoxic conditions can increase HIF‐2α levels and lead to impaired Treg cell function, but does not affect the expression of Foxp3 181 . Similarly, HIF‐2α‐mediated Treg cell dysfunction may also be involved in airway hypersensitivity 182 .…”

Section: Effect Of Hypoxia On Immune Cellsmentioning

confidence: 99%

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The role of hypoxia in the pathophysiology of chronic rhinosinusitis

Zhong

Seah

Liu

et al. 2022

Allergy

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Chronic rhinosinusitis (CRS) is characterized by inflammation of the nasal cavity and the paranasal sinuses. [1][2][3][4] It has a significant impact on living and working conditions, affecting about 5%-12% of the general population. [5][6][7] Common complaints of such patients include nasal congestion, nasal discharge, altered sense of smell, facial pain, and facial pressure. The United States conservatively estimates that spending on CRS amounts up to $30 billion each year, inevitably creating a huge economic burden on society. 7 From an etiological point of view, CRS can be classified into primary and secondary forms. 8 Primary CRS is characterized by chronic inflammation of the nasal cavity and paranasal sinuses, where an obvious secondary causative factor is absent. Secondary

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Metabolic factors contribute to T‐cell inhibition in the ovarian cancer ascites

Gong

Yang

Wang

et al. 2020

Intl Journal of Cancer

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Malignant ascites is one of the major clinical features of ovarian cancer, which serves as a carrier for the peritoneal dissemination of tumor cells and predicts a poor prognosis in patients. In the microenvironment of ovarian cancer ascites, antitumor immunity is suppressed, which enables the tumor cells to escape from immune surveillance. The metabolic factors, including hypoxia, nutrient deprivation and accumulation of metabolic products, contribute to the immunosuppressive status of malignant ascites. The malignant ascites and ovarian solid tumors exhibit differential metabolic profiles. In this review, we have summarized the most recent findings on the interaction between immune cells and metabolic factors in the ovarian cancer ascites. The effects of metabolic factors on the antitumor functions of T‐cells in the malignant ascites were analyzed. Finally, we have discussed the potential directions for future research in this field.

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A PHD in immunosuppression: oxygen-sensing pathways regulate immunosuppressive Tregs

Cited by 6 publications

References 23 publications

Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity

Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity

The role of hypoxia in the pathophysiology of chronic rhinosinusitis

Metabolic factors contribute to T‐cell inhibition in the ovarian cancer ascites

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