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The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducting resolution of inflammation

ABSTRACT: The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducting resolution of inflammation

PROVIDER: PRJNA857490 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20074378_1.fastq.gz	Fastqsanger.gz
	SRR20074378_2.fastq.gz	Fastqsanger.gz
	SRR20074379_1.fastq.gz	Fastqsanger.gz
	SRR20074379_2.fastq.gz	Fastqsanger.gz
	SRR20074380_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducting resolution of inflammation

Project description:Here we show that soluble CD83 induces resolution of inflammation in the antigen-induced arthritis (AIA) model. Joint swelling as well as arthritis related expression levels of IL‐1β, IL‐6, RANKL, MMP9 and OC‐Stamp were strongly reduced, while Foxp3 was induced. In addition, we observed a significant inhibition of TRAP+ osteoclast formation, correlating with the reduced arthritic disease score. In contrast, cell specific deletion of CD83 in human and murine precursor cells resulted in an enhanced formation of mature osteoclasts. RNA-sequencing analyses, comparing sCD83- with mock treated cells, revealed a strong downregulation of osteoclastogenic factors, such as OC-STAMP, MMP9, NFATC1, Ctsk and Trap. Concomitantly, transcripts typical for pro-resolving macrophages, e.g. Mrc1/2, Marco, Klf4 and Mertk, were upregulated. Interestingly, also members of the metallothionein (MT) family, which have been associated with a reduced arthritic disease severity, were highly induced by sCD83 also in samples derived from RA patients. Finally, we elucidated the sCD83-induced signalling cascade, downstream to its binding to the Toll-like receptor 4/(TLR4/MD2) receptor complex, using CRISPR/Cas9-induced knockdowns of TLR4/MyD88/TRIF and MTs, revealing that sCD83 acts via the TRIF-signalling cascade. In conclusion, sCD83 represents a promising therapeutic approach to induce resolution of inflammation and to prevent bone erosion in autoimmune arthritis.

2022-07-13 | GSE207872 | GEO

Soluble CD83 modulates human-monocyte-derived macrophages towards alternative phenotype, function and metabolism

Project description:Soluble CD83 modulates human-monocyte-derived macrophages towards alternative phenotype, function and metabolism

| PRJNA1029907 | ENA

Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages

Project description:Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages

| PRJNA883724 | ENA

Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages

Project description:To facilitate the recovery process of chronic and hard-to-heal wounds novel pro-resolving treatment options are urgently needed. We investigated the pro regenerative properties of soluble CD83 (sCD83) on cutaneous wound healing, where sCD83 accelerated wound healing not only after systemic but also after topical application, which is of high therapeutic interest. Cytokine profile analyses revealed an initial upregulation of inflammatory mediators such as TNFa and IL-1b, followed by a switch towards pro-resolving factors, including YM-1 and IL-10, both expressed by tissue repair macrophages. These cells are known to mediate resolution of inflammation and stimulate wound healing processes by secretion of growth factors such as epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), which promote vascularization as well as fibroblast and keratinocyte differentiation. In conclusion, we have found strong wound healing capacities of sCD83 beyond the previously described role in transplantation and autoimmunity. This makes sCD83 a promising candidate for the treatment of chronic- and hard-to-heal wounds

2022-09-30 | GSE214079 | GEO

Soluble CD83 modulates human-monocyte-derived macrophages towards alternative phenotype, function and metabolism

Project description:Alterations in macrophage (Mφ) polarization, function and metabolic signature can foster development of chronic diseases, such as autoimmunity, or fibrotic tissue remodeling. Thus, identification of novel therapeutic agents that modulate human Mφ biology is crucial for treatment of such conditions. Herein we demonstrate that the soluble CD83 (sCD83) protein induces pro-resolving features in human monocyte-derived Mφ biology. We show that sCD83 strikingly increases the expression of inhibitory molecules including ILT-2 (immunoglobulin-like transcript 2), ILT-4, ILT-5 and CD163, whilst activation markers, such as MHC-II and MSR-1 were significantly downregulated. This goes along with a decreased capacity to stimulate alloreactive T cells in mixed lymphocyte reaction (MLR) assays. Bulk RNA sequencing and pathway analyses revealed that sCD83 downregulates pathways associated with pro-inflammatory, classically-activated Mφ (CAM) differentiation including HIF-1A, IL-6 as well as cytokine storm, whilst pathways related to alternative Mφ activation and Liver X receptor were significantly induced. By using the LXR pathway antagonist GSK2033, we show that transcription of specific genes (e.g. PPARG, ABCA1, ABCG1, CD36) induced by sCD83 are dependent on LXR activation. In summary, we herein reveal for the first time mechanistic insights into the modulation of human Mφ biology by sCD83, which is a further crucial pre-clinical study for the establishment of sCD83 as a new therapeutical agent to treat inflammatory conditions.

2023-12-14 | GSE245761 | GEO

Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts

Project description:The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signaling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P3. Finally, pharmacologic treatment with the non-selective S1P receptor agonist FTY720 causes increased bone formation in wildtype, but not in S1P3-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo, and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts. Osteoclasts of wildtype and Calcr-/- C57Bl/6 mice were treated with Calcitonin and compared to the non-treated osteoclasts of wildtype or Calcr-/- mice, respectively.

2014-10-19 | E-GEOD-60761 | biostudies-arrayexpress

JAK inhibition ameliorates bone destructions by simultaneously targeting mature osteoclasts and their precursor stages

Project description:Inflammatory bone destruction was induced by locally injecting lipopolysaccharides into fluorescent reporter mice of mature osteoclasts or their precursors. These mice were treated with a JAK inhibitor, ABT-317, which selectively inhibits the activation of JAK1, and intravital imaging with multiphoton microscopy was conducted. We also investigated the molecular mechanism of the effects of the JAK inhibitor on osteoclasts by exhaustive RNA sequence analysis.

2023-03-05 | GSE193104 | GEO

Microglial expression of CD83 governs cellular activation and restrains autoimmune neuroinflammation

Project description:Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue and the initial response of microglia determines the severity of neuroinflammatory diseases. CD83 has been associated with early activation of microglia in various disease settings albeit its functional relevance for microglial biology was still elusive. Thus, we conducted a thorough assessment of CD83 regulation in microglia as well as its impact on microglial mediated neuroinflammation. Here, we describe for the first time that CD83 expression in microglia is not only associated with cellular activation but also with pro-resolving functions. Conditional deletion of CD83 causes malfunctioning responses to myelin debris, which results in an over-activated state during autoimmune neuroinflammation. Subsequently, CD83-deficient microglia recruit more pathogenic immune cells to the central nervous system and deteriorate resolving mechanism, which exacerbates the disease. Thus, CD83 in microglia orchestrates cellular activation and consequently, also resolution of neuroinflammation.

2023-06-28 | GSE230753 | GEO

The Role of CD83 in ovarian cancer cell line SKOV3

Project description:We performed RNA-Seq of CD83 overexpression SKOV3 cells (OV_1, OV_2, OV_3), CD83 knockdown SKOV3 cells (KD_1, KD_2, KD-3), and control SKOV3 cells (NC_1, NC_2, NC_3) using BGISEQ-500 platform (BGI, China).

2019-01-14 | GSE125011 | GEO

Murine Osteoclasts: Stat5 flox vs. Stat5 cKO

Project description:Transcriptional profiling of mouse osteoclasts comparing control osteoclasts from Stat5 flox mice with osteoclasts from Stat5 cKO mice. Two-condition experiment, Stat5 flox cells vs. Stat5 cKO cells

2013-12-09 | E-GEOD-51283 | biostudies-arrayexpress

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