Decrease in circulating plasmacytoid dendritic cells during short‐term systemic normobaric hypoxia

Yılmaz, Atilla; Ratka, Josi; Rohm, Ilonka; Pistulli, Rudin; Goebel, Björn; Asadi, Yahya; Petri, Alexander; Kiehntopf, Michael; Figulla, Hans R.; Jung, Christian

doi:10.1111/eci.12416

Cited by 14 publications

(9 citation statements)

References 29 publications

(39 reference statements)

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“…At an altitude of 3,000 m, the number of circulating dendritic cells in human plasma is significantly reduced ( 36 ). At an altitude of 5,000 m, plasmacytoid dendritic cells in human plasma are reduced, and the TNF-α and IL-6 contents are significantly increased ( 37 ). We found that several genes, including NKIRAS2, IKBKE, and TRIM7, were involved in immunoregulation and were lncRNA target genes ( 38 – 40 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Long Non-coding RNA and mRNA Transcriptomes Related to Hypoxia Adaptation in Tibetan Sheep

Yuan

et al. 2022

Front. Vet. Sci.

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Tibetan sheep have lived on the Qinghai-Tibet Plateau for a long time, and after long-term natural selection, they have shown stable genetic adaptability to high-altitude environments. However, little is known about the molecular mechanisms of the long non-coding (lnc)RNAs involved in the adaptation of Tibetan sheep to hypoxia. Here, we collected lung tissues from high-altitude Tibetan sheep and low-altitude Hu sheep for RNA sequencing to study the regulatory mechanisms of the lncRNAs and mRNAs in the adaptation of Tibetan sheep to hypoxia. We identified 254 differentially expressed lncRNAs and 1,502 differentially expressed mRNAs. We found 20 pairs of cis-regulatory relationships between 15 differentially expressed lncRNAs and 14 protein-coding genes and two pairs of trans-regulatory relationships between two differentially expressed lncRNAs and two protein-coding genes. These differentially expressed mRNAs and lncRNA target genes were mainly enriched in pathways related to lipid metabolism and immune function. Interaction network analysis showed that 17 differentially expressed lncRNAs and 15 differentially expressed mRNAs had an interactive relationship. Additionally, we used six differentially expressed lncRNAs and mRNAs to verify the accuracy of the sequencing data via qRT-PCR. Our results provide a comprehensive overview of the expression patterns of the lncRNAs and mRNAs involved in the adaptation of Tibetan sheep to hypoxia, laying a foundation for further analysis of the adaptations of plateau animals.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of Long Non-coding RNA and mRNA Transcriptomes Related to Hypoxia Adaptation in Tibetan Sheep

Yuan

et al. 2022

Front. Vet. Sci.

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“…In some reports, hypoxia increases the ability of DCs to interact with cytotoxic T cells [159]. Hypoxia has been shown to decrease circulating plasmacytoid DCs with corresponding increase in TNF‐α and IL‐6, although increase in CXCL12 could signify tissue migration [160]. One experiment demonstrated that DCs without HIF‐1α had less CD278 on their cell surface, and the T cells in co‐culture produced less granzyme B mRNA [161].…”

Section: Dendritic Cellsmentioning

confidence: 99%

Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma

Daniel

Sullivan

Labadie

et al. 2019

Clinical & Translational Med

164

109

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Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with limited response to cytotoxic chemoradiotherapy, as well as newer immunotherapies. The PDA tumor microenvironment contains infiltrating immune cells including cytotoxic T cells; however, there is an overall immunosuppressive milieu. Hypoxia is a known element of the solid tumor microenvironment and may promote tumor survival. Through various mechanisms including, but not limited to, those mediated by HIF-1α, hypoxia also leads to increased tumor proliferation and metabolic changes. Furthermore, epithelial to mesenchymal transition is promoted through several pathways, including NOTCH and c-MET, regulated by hypoxia. Hypoxia-promoted changes also contribute to the immunosuppressive phenotype seen in many different cell types within the microenvironment and thereby may inhibit an effective immune system response to PDA. Pancreatic stellate cells (PSCs) and myofibroblasts appear to contribute to the recruitment of myeloid derived suppressor cells (MDSCs) and B cells in PDA via cytokines increased due to hypoxia. PSCs also increase collagen secretion in response to HIF-1α, which promotes a fibrotic stroma that alters T cell homing and migration. In hypoxic environments, B cells contribute to cytotoxic T cell exhaustion and produce chemokines to attract more immunosuppressive regulatory T cells. MDSCs inhibit T cell metabolism by hoarding key amino acids, modulate T cell homing by cleaving L-selectin, and prevent T cell activation by increasing PD-L1 expression. Immunosuppressive M2 phenotype macrophages promote T cell anergy via increased nitric oxide (NO) and decreased arginine in hypoxia. Increased numbers of regulatory T cells are seen in hypoxia which prevent effector T cell activation through cytokine production and increased CTLA-4. Effective immunotherapy for pancreatic adenocarcinoma and other solid tumors will need to help counteract the immunosuppressive nature of hypoxia-induced changes in the tumor microenvironment. Promising studies will look at combination therapies involving checkpoint inhibitors, chemokine inhibitors, and possible targeting of hypoxia. While no model is perfect, assuring that models incorporate the effects of hypoxia on cancer cells, stromal cells, and effector immune cells will be crucial in developing successful therapies.

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“…By profiling a large number of immune molecules using Luminex array, we identified multiple molecular changes associated with systemic hypoxia, some of which have been previously reported in humans and animals exposed to hypoxia. For example, elevated blood levels of IL-6, TNF-α and IL-1β have been reported in high-altitude-associated hypoxia [35] and in experimental hypoxia [51][52][53][54][55][56][57][58] using enzymelinked immunosorbent assay (ELISA) to measure a small number of cytokines. In the retina, we found that 4 molecules were upregulated in systemic hypoxia: VEGF, IL-1β, IL-22, and MCP3.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes

et al. 2021

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Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology. We induced severe systemic hypoxia in adult C57BL/6 mice using a hypoxia chamber (10% O2) for 1 week and rapidly assessed measurements within 1h compared with 18h after hypoxia. Optical coherence tomography revealed retinal tissue edema at 18h after hypoxia. Hierarchical clustering of plasma and retinal immune molecules revealed obvious segregation of the 1h posthypoxia group away from that of controls. One hour after hypoxia, there were 10 significantly increased molecules in plasma and 4 in retina. Interleukin-1β and vascular endothelial growth factor were increased in both tissues. Concomitantly, there was significantly increased aquaporin-4, decreased Kir4.1, and increased gliosis in retinal histology. In summary, the immediate posthypoxic period is characterized by molecular changes consistent with systemic and retinal inflammation and retinal glial changes important in water transport, leading to tissue edema. This posthypoxic inflammation rapidly improves within 24h, consistent with the typically mild and transient visual disturbance in hypoxia, such as in high-altitude retinopathy. Given hypoxia increases risk of vision loss, more studies in at-risk patients, such as plasma immune profiling and in vivo retinal imaging, are needed in order to identify novel diagnostic or prognostic biomarkers of visual impairment in systemic hypoxia.

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Decrease in circulating plasmacytoid dendritic cells during short‐term systemic normobaric hypoxia

Abstract: We show a significant decrease in circulating pDCs during hypoxia in parallel to a pro-inflammatory response. Further studies are necessary to evaluate whether the decrease in circulating pDCs might be the result of an enhanced tissue recruitment.

Cited by 14 publications

References 29 publications

Comprehensive Analysis of Long Non-coding RNA and mRNA Transcriptomes Related to Hypoxia Adaptation in Tibetan Sheep

Comprehensive Analysis of Long Non-coding RNA and mRNA Transcriptomes Related to Hypoxia Adaptation in Tibetan Sheep

Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma

Hypoxia-induced inflammation: Profiling the first 24-hour posthypoxic plasma and central nervous system changes

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