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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

The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducing resolution of inflammation in arthritis.

Project description:Here we show that soluble CD83 induces the resolution of inflammation in an antigen-induced arthritis (AIA) model. Joint swelling and the 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 and Nfatc1, Ctsk, and Trap. Concomitantly, transcripts typical for pro-resolving macrophages, e.g., Mrc1/2, Marco, Klf4, and Mertk, were upregulated. Interestingly, members of the metallothionein (MT) family, which have been associated with a reduced arthritic disease severity, were also highly induced by sCD83 in samples derived from RA patients. Finally, we elucidated the sCD83-induced signaling 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-signaling cascade. In conclusion, sCD83 represents a promising therapeutic approach to induce the resolution of inflammation and to prevent bone erosion in autoimmune arthritis.

| S-EPMC9393726 | biostudies-literature

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

SerpinA3N limits cartilage destruction in osteoarthritis by inhibiting macrophage-derives leukocyte elastase

Project description:SerpinA3N limits cartilage destruction in osteoarthritis by inhibiting macrophage-derives leukocyte elastase

| PRJNA1130070 | ENA

Cd83

Project description:Rattus norvegicus Cd83, CD83 molecule [Source:RGD Symbol;Acc:1309677], is expressed in 4 baseline experiment(s);

| ENSRNOG00000018092 | ExpressionAtlas

Cd83

Project description:Rattus norvegicus Cd83, CD83 molecule [Source:RGD Symbol;Acc:1309677], is differentially expressed in 21 experiment(s);

| ENSRNOG00000018092 | ExpressionAtlas

Cd83

Project description:Mus musculus Cd83, CD83 antigen [Source:MGI Symbol;Acc:MGI:1328316], is differentially expressed in 130 experiment(s);