Endothelial Sox17 promotes allergic airway inflammation

Ha, Eun Hee; Choi, Jun-Pyo; Kwon, Hyouk‐Soo; Park, Hyeung Ju; Lah, Sang Joon; Moon, Keun‐Ai; Lee, Seung‐Hyo; Kim, Injune; Cho, You Sook

doi:10.1016/j.jaci.2019.02.034

Cited by 14 publications

(10 citation statements)

References 51 publications

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“…SOX17 is known as a transcriptional regulator that orchestrates arterial specification, endothelial integrity and modulates tip cell differentiation during vessel sprouting [ 51 , 52 , 53 ]. In line with the co-expression of ICAM1 and SOX17 in the PVC cluster, it has recently been shown that the level of SOX17 was markedly elevated in ECs upon inflammation, which was essential to the induction of ICAM1 expression and monocyte adhesion [ 54 ]. Arterioles and post-arterial capillaries share a high level of molecular similarities.…”

Section: Discussionmentioning

confidence: 99%

Novel Blood Vascular Endothelial Subtype-Specific Markers in Human Skin Unearthed by Single-Cell Transcriptomic Profiling

Tacconi

Kim

et al. 2022

Cells

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Ample evidence pinpoints the phenotypic diversity of blood vessels (BVs) and site-specific functions of their lining endothelial cells (ECs). We harnessed single-cell RNA sequencing (scRNA-seq) to dissect the molecular heterogeneity of blood vascular endothelial cells (BECs) in healthy adult human skin and identified six different subpopulations, signifying arterioles, post-arterial capillaries, pre-venular capillaries, post-capillary venules, venules and collecting venules. Individual BEC subtypes exhibited distinctive transcriptomic landscapes associated with diverse biological pathways. These functionally distinct dermal BV segments were characterized by their unique compositions of conventional and novel markers (e.g., arteriole marker GJA5; arteriole capillary markers ASS1 and S100A4; pre-venular capillary markers SOX17 and PLAUR; venular markers EGR2 and LRG1), many of which have been implicated in vascular remodeling upon inflammatory responses. Immunofluorescence staining of human skin sections and whole-mount skin blocks confirmed the discrete expression of these markers along the blood vascular tree in situ, further corroborating BEC heterogeneity in human skin. Overall, our study molecularly refines individual BV compartments, whilst the identification of novel subtype-specific signatures provides more insights for future studies dissecting the responses of distinct vessel segments under pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Novel Blood Vascular Endothelial Subtype-Specific Markers in Human Skin Unearthed by Single-Cell Transcriptomic Profiling

Tacconi

Kim

et al. 2022

Cells

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“…In addition to NF-κB-dependent transactivation by TRIM28, RIPK3-mediated sequestration of TRIM28 from the chromatin can release repression on SOX9 transcriptional activity. SOX9-mediated repression of its target genes through TRIM28 was recently reported [ 45 ] and other SOX family members were also shown to correlate with activation or repression of TRIM28 target genes [ 46 , 47 ]. From SOX9 ChIP-Seq data, we can speculate that reduced TRIM28 binding from chromatin during TSZ stimulation may turn on SOX9-mediated transactivation to express cytokines.…”

Section: Discussionmentioning

confidence: 99%

RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment

et al. 2021

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Background Necroptosis is emerging as a new target for cancer immunotherapy as it is now recognized as a form of cell death that increases tumor immunogenicity, which would be especially helpful in treating immune-desert tumors. De novo synthesis of inflammatory proteins during necroptosis appears especially important in facilitating increased anti-tumor immune responses. While late-stage transcription mediated by NF-κB during cell death is believed to play a role in this process, it is otherwise unclear what cell signaling events initiate this transactivation of inflammatory genes. Methods We employed tandem-affinity purification linked to mass spectrometry (TAP-MS), in combination with the analysis of RNA-sequencing (RNA-Seq) datasets to identify the Tripartite Motif Protein 28 (TRIM28) as a candidate co-repressor. Comprehensive biochemical and molecular biology techniques were used to characterize the role of TRIM28 in RIPK3 activation-induced transcriptional and immunomodulatory events. The cell composition estimation module was used to evaluate the correlation between RIPK3/TRIM28 levels and CD8+ T cells or dendritic cells (DC) in all TCGA tumors. Results We identified TRIM28 as a co-repressor that regulates transcriptional activity during necroptosis. Activated RIPK3 phosphorylates TRIM28 on serine 473, inhibiting its chromatin binding activity, thereby contributing to the transactivation of NF-κB and other transcription factors, such as SOX9. This leads to elevated cytokine expression, which then potentiates immunoregulatory processes, such as DC maturation. The expression of RIPK3 has a significant positive association with the tumor-infiltrating immune cells populations in various tumor type, thereby activating anti-cancer responses. Conclusion Our data suggest that RIPK3 activation-dependent derepression of TRIM28 in cancer cells leads to increased immunostimulatory cytokine production in the tumor microenvironment, which then contributes to robust cytotoxic anti-tumor immunity.

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“…The vascular factor plays an important role in the development of the allergic process in the lungs. Endothelial cells express P-selectin, E-selectin, Sox17, intercellular adhesion molecules-1 (ICAM-1) and blood cell adhesion molecules (VCAM-1) [11]. On the other hand, the components of the vascular wall (endothelium, smooth myocytes, fibroblasts) are targets for neuroendocrine [12] and immune factors [10] of the development of allergic process in the lungs.…”

Section: Discussionmentioning

confidence: 99%

Morphological rearrangement of the metabolic link of the microcirculatory bed of guinea pigs lungs after sensitization with ovalbumin

Попко¹

2021

АПФМНП

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The reaction of the lung microvessels is an urgent issue of morphology and medicine in general, as well as one of the insufficiently investigated points in the study of morphological changes in chronic allergic diseases of the respiratory system. The aim is to study the morphological changes in the vessels of the metabolic link of the microcirculation in the lungs of guinea pigs sensitized with ovalbumin. Materials and methods. We have studied the lungs of 48 guinea pigs, using histological and morphometric methods, under conditions of experimental ovalbumin-induced allergic inflammation, simulated by three-time subcutaneous sensitization and subsequent 8-day intranasal inhalation of ovalbumin. To estimate the structural and functional state of capillaries, the inner diameter of the vessels was determined. Results. A general regularity in the reactivity of the hemomicrocirculatory bed of guinea pig lungs in experimental ovalbumin-induced allergic inflammation was established, which consists in a significant structural and functional restructuring of the exchange vessels of the microcirculatory bed. Dysfunction of the capillaries endothelium is manifested by a change of vasodilatation to vasospasm, as evidenced by morphometric changes in the diameter of the capillaries lumen in the experimental groups, and an increase in the permeability of the capillaries wall, which is confirmed by edema and disorganization of the connective tissue component. Conclusions. Allergic inflammation leads to structural and functional reorganization of the metabolic link of the hemomicrocirculatory bed of guinea pig lungs, which has a multidirectional staging character depending on the duration of the experiment and is a manifestation of a violation of the compensatory-adaptive processes of hemomicrocirculation. The most pronounced changes in the form of a decrease in the diameter of the lumen of the blood capillaries of the lungs of guinea pigs by 23 % compared to the control are observed during the late period of the development of the allergic inflammatory process.

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Endothelial Sox17 promotes allergic airway inflammation

Cited by 14 publications

References 51 publications

Novel Blood Vascular Endothelial Subtype-Specific Markers in Human Skin Unearthed by Single-Cell Transcriptomic Profiling

Novel Blood Vascular Endothelial Subtype-Specific Markers in Human Skin Unearthed by Single-Cell Transcriptomic Profiling

RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment

Morphological rearrangement of the metabolic link of the microcirculatory bed of guinea pigs lungs after sensitization with ovalbumin

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