Analysis of serum-derived and internalized complement component C3 bound DNA sequences
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ABSTRACT:
PROVIDER: PRJEB30321 | ENA |
REPOSITORIES: ENA
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Project description:The aim of this study was to identify genes/DNA sequences which serum-derived and internalized C3 might interact with in the human B lymphoblastoma cell line, Raji. The project involved analysis of the proteins’ uptake from the serum, the verification of its nuclear entry and identification of the potential interacting nucleic acid sequences by ChIPsequencing.
2019-12-31 | E-MTAB-7506 | biostudies-arrayexpress
Project description:The most abundant and central component, glycoprotein C3, contributes to the development of type 1 diabetes by enhancing the organ-specific autoimmune inflammatory processes. It is known that changes in glycosylation can modulate inflammatory responses and we recently showed that children at the onset of type 1 diabetes have a higher proportion of oligomannose glycans in plasma N-glycome compared to their healthy siblings. Due to fact that C3 contains two N-glycosylation sites occupied by this type of glycans, our aim was to develop a novel high-throughput and cost-effective glycoproteomic workflow for N-glycosylation analysis of human C3 to reveal the possible role of C3 glycosylation in type 1 diabetes development.
2023-03-10 | PXD034083 | Pride
Project description:The most abundant and central component, glycoprotein C3, contributes to the development of type 1 diabetes by enhancing the organ-specific autoimmune inflammatory processes. It is known that changes in glycosylation can modulate inflammatory responses and we recently showed that children at the onset of type 1 diabetes have a higher proportion of oligomannose glycans in plasma N-glycome compared to their healthy siblings. Due to fact that C3 contains two N-glycosylation sites occupied by this type of glycans, our aim was to develop a novel high-throughput and cost-effective glycoproteomic workflow for N-glycosylation analysis of human C3 to reveal the possible role of C3 glycosylation in type 1 diabetes development.
2023-03-11 | PXD035126 | Pride
Project description:We performed scRNAseq analysis of CD45- cells sorted from murine brains on the presence or absence of a fluorescent reporter for complement component C3 at peak of experimental autoimmune encephalomyelitis to study the non-immune cellular sources of C3
2024-02-01 | GSE254863 | GEO
Project description:Perioperative neurocognitive disorder (PNDs) can commonly occur after major surgery in at risk patients and its occurrence increases medical healthcare burdens and even mortality. Accumulating evidence points to neuroinflammation being pivotal to the pathogenesis of these conditions. The complement cascade contributes to neuroinflammatory responses in the central nervous system (CNS) and complement C3 has been implicated in the manifestation of cognitive deficits in several neurological conditions. Neurotoxic reactive astrocytes function differently to their non-activated counterparts and release complement components in response to pathological triggers. We observed previously that surgery induces a rapid rise and then fall in cytokines but a more sustained glial activation response that coincided with postoperative cognitive impairment. In this study, we explored the relationship between the expression of complement C3, glial activation, and cognitive deficits. Using a murine model of surgery, we characterized the transcriptional profiles of hippocampal astrocytes after surgery and examined the effects of C3 suppression on the neuroinflammatory response and cognitive performance. There was a delayed but sustained rise in hippocampal C3 of astrocytic in origin after surgery which corresponded with the onset of cognitive decline. Furthermore, the A1 or the neurotoxic phenotype predominated in this postoperative astrocytic activation, and these cells have a distinct transcriptional profile including C3 upregulation. Suppression of C3 inhibited synaptic phagocytosis by microglia and attenuated postoperative cognitive impairment. Therefore, C3 from reactive astrocytes appear central to the development of cognitive dysfunction associated with postoperative neuroinflammation.
2024-03-13 | GSE199318 | GEO
Project description:Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption the GAPAID consortium examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n=211), with other systemic autoimmune diseases (n=65) and non-autoimmune control subjects (n=149) in two rheumatology tertiary care centers. Standard clinical and laboratory data were collected from all subjects and serum complement levels were determined in SLE patients. The genotype of SNP rs1143679 in the ITGAM gene was also determined. On-chip formation of immune complexes was examined using a functional immunoassay on autoantigen microarray. The amount of antigen-bound IgM, IgG and complement C4 and C3 was quantified on autoantigens comprising nucleic acids, proteins and lipids. Our results show that the relatively high complement consumption of nucleic acids is further increased upon binding of IgM and IgG. This is true even when serum complement levels are decreased due to complement consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, most protein and lipid autoantigens show positive correlation with C4 and C3 levels. Genetic analysis reveals that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) have lower levels of dsDNA specific IgM among SLE patients. Regarding organ involvement we find that besides anti-C1q IgG, low levels of dsDNA specific IgM and low complement C4 binding to C1q are also associated with renal injury. In summary, nucleic acids maintain a skewed complement deposition balance when bound by IgG and IgM, depleting the early classical complement pathway from other physiological processes. Dysfunction of the receptor responsible for complement-mediated apoptotic debris removal promotes the development of autoantibodies targeting nucleic acids. These observations provide serological and genetic evidence for complement-mediated clearance deficiency of apoptotic debris in lupus.
2016-03-07 | GSE69365 | GEO
Project description:Rhabdomyolysis is a severe condition caused by skeletal muscle damage, leading to acute kidney injury (AKI). We demonstrate that complement has a direct pathogenic role in rhabdomyolysis-induced AKI. Deposition of C3d in the tubules of patients and mice correlated with rhabdomyolysis-induced AKI. Moreover, C3-defiient mice with rhabdomyolysis had preserved renal function. Mechanistically, C3-deficiency attenuated strongly inflammatory and apoptotic components of the renal transcriptome, perturbed by rhabdomyolysis. Complement was activated intrarenal by the lectin pathway via collectin-11. It proceeded in a C4-bypass manner and was amplified by heme-activated alternative pathway. Therefore, complement and heme are promising therapeutic targets for rhabdomyolysis-induced AKI.
2020-11-01 | GSE153507 | GEO
Project description:Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization, is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host’s specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as a novel innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.
2024-01-16 | GSE250268 | GEO
Project description:Canonically, the complement system is known for its rapid response to remove microbes in the bloodstream. However, relatively little is known about a functioning complement system on intestinal mucosal surfaces. Herein we report the local synthesis of complement component 3 (C3) in the gut, primarily by stromal cells. C3 is expressed upon commensal colonization, is regulated by the composition of the microbiota in healthy humans and mice, leading to an individual host’s specific luminal C3 levels. The absence of membrane attack complex (MAC) components in the gut ensures that C3 deposition does not result in the lysis of commensals. Pathogen infection triggers the immune system to recruit neutrophils to the infection site for pathogen clearance. Basal C3 levels directly correlate with protection against enteric infection. Our study reveals the gut complement system as a novel innate immune mechanism acting as a vigilant sentinel that combats pathogens and spares commensals.
2023-12-04 | GSE248940 | GEO
Project description:Mounting evidence has highlighted the importance of complement in the construction of an immunosuppressive tumor microenvironment (TME). Tumor cell-derived C3 has been previously reported, however, whether and how it acts on anti-tumor immunity remains to be elucidated. Here, we describe a unique role of tumor cell-derived C3 in suppressing anti-tumor immunity. Tumor cell-derived C3 was activated intracellularly, which results in generation of C3a. C3a could modulate tumor-associated macrophages (TAMs) via C3a-C3aR-PI3Kγ signaling, thereby repressing anti-tumor immunity. More importantly, deletion of C3 in tumor cells with high C3 expression is sufficient to enhance the efficacy of ɑPD-L1 treatment. Collectively, our present results suggest tumor cell-derived C3 may serve as a novel target in cancer immunotherapy, specifically targeting C3 in tumor cells to enhance anti-tumor immunity.
2018-09-21 | GSE120274 | GEO