Soluble CD83 improves and accelerates wound healing by the induction of pro-resolving macrophages
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ABSTRACT:
PROVIDER: PRJNA883724 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21685975_1.fastq.gz | Fastqsanger.gz | |||
| SRR21685975_2.fastq.gz | Fastqsanger.gz | |||
| SRR21685976_1.fastq.gz | Fastqsanger.gz | |||
| SRR21685976_2.fastq.gz | Fastqsanger.gz | |||
| SRR21685977_1.fastq.gz | Fastqsanger.gz |
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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
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 TNFα and IL-1β, 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.
| S-EPMC9564224 | biostudies-literature
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
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
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
Project description:Soluble CD83 modulates human-monocyte-derived macrophages towards alternative phenotype, function and metabolism
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Project description:Clearance of p21-highly-expressing senescent cells accelerates wound healing
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Project description:Defective fibroblast migration cause delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective treatment able to improve wound healing capacity. However, the molecular mechanisms connecting their beneficial outcomes with the wound healing process are still unrevealed. Here, we show that AMG modulates primary fibroblast migration and accelerates skin re-epithelialization without affecting cell proliferation. We demonstrate that AMG is enriched in a pool of WH-associated growth factors that may provide the initiation signal for faster endogenous wound healing response. This, in turn leads to increased cell migration rate by elevating activity of ERK and subsequent activation of matrix metalloproteinase expression and their extracellular enzymatic activity. Moreover, AMG-treated wounds showed increased granulation tissue formation and organized collagen content. Overall, we shed light on AMG molecular mechanism supporting its potential to trigger highly improved wound healing process.
2020-01-01 | GSE123829 | GEO
Project description:The soluble CD83 protein prevents bone destruction by inhibiting the formation of osteoclasts and inducting resolution of inflammation
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Project description:Poorly healing diabetic wounds are characterized by diminished collagen production and impaired angiogenesis. HoxD3, a homeobox transcription factor that promotes angiogenesis and collagen synthesis, is up-regulated during normal wound repair whereas its expression is diminished in poorly healing wounds of the genetically diabetic (db/db) mouse. To determine whether restoring expression of HoxD3 would accelerate diabetic wound healing, we devised a novel method of gene transfer, which incorporates HoxD3 plasmid DNA into a methylcellulose film that is placed on wounds created on db/db mice. The HoxD3 transgene was expressed in endothelial cells, fibroblasts, and keratinocytes of the wounds for up to 10 days. More importantly, a single application of HoxD3 to db/db mice resulted in a statistically significant acceleration of wound closure compared to control-treated wounds. Furthermore, we also observed that the HoxD3-mediated improvement in diabetic wound repair was accompanied by increases in mRNA expression of the HoxD3 target genes, Col1A1 and beta 3-integrin leading to enhanced angiogenesis and collagen deposition in the wounds. Although HoxD3-treated wounds also show improved re-epithelialization as compared to control db/db wounds, this effect was not due to direct stimulation of keratinocyte migration by HoxD3. Finally, we show that despite the dramatic increase in collagen synthesis and deposition in HoxD3-treated wounds, these wounds showed normal remodeling and we found no evidence of abnormal wound healing. These results indicate that HoxD3 may provide a means to directly improve collagen deposition, angiogenesis and closure in poorly healing diabetic wounds.
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