CD22 blockage restores age-related impairments of microglia surveillance capacity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE169252 | GEO | 2021/03/30
REPOSITORIES: GEO
Similar Datasets
Project description:CD22 blockage restores age-related impairments of microglia surveillance capacity
| PRJNA715777 | ENA
Project description:Microglia, the innate immune cells of the brain, are essential for maintaining homeostasis by their ramified, highly motile processes and for orchestrating the immune response to pathological stimuli. They are implicated in several neurodegenerative diseases like Alzheimer's and Parkinson's disease. One commonality of these diseases is their strong correlation with aging as the highest risk factor and studying age-related alterations in microglia physiology and associated signaling mechanism is indispensable for a better understanding of age-related pathomechanisms. CD22 has been identified as a modifier of microglia phagocytosis in a recent study, but not much is known about the function of CD22 in microglia. Here we show that CD22 surface levels are upregulated in aged versus adult microglia. Furthermore, in the amyloid mouse model PS2APP, Aβ-containing microglia also exhibit increased CD22 signal. To assess the impact of CD22 blockage on microglia morphology and dynamics, we have established a protocol to image microglia process motility in acutely prepared brain slices from CX3CR1-GFP reporter mice. We observed a significant reduction of microglial ramification and surveillance capacity in brain slices from aged versus adult mice. The age-related decrease in surveillance can be restored by antibody-mediated CD22 blockage in aged mice, whereas surveillance in adult mice is not affected by CD22 inhibition. Moreover to complement the results obtained in mice, we show that human iPSC-derived macrophages exhibit an increased phagocytic capacity upon CD22 blockage. Downstream analysis of antibody-mediated CD22 inhibition revealed an influence on BMP and TGFβ associated gene networks. Our results demonstrate CD22 as a broad age-associated modulator of microglia functionality with potential implications for neurodegenerative disorders.
| S-EPMC8204252 | biostudies-literature
Project description:CD22 (Siglec-2) is a member of the Siglec family. It is an inhibitory co-receptor of the B-cell-receptor (BCR) and inhibits B–cell activation. Upon BCR stimulation ITIMs in the cytoplasmic tail of CD22 are phosphorylated. This triggers CD22 signalling pathways, which lead to a decreased calcium mobilization in the B cell and thus an inhibition of BCR signalling. Although some CD22 binding partners, such as the phosphatase SHP-1, have already been identified, we deciphered the CD22 interactome in more detail, to gain a deeper understanding of CD22 molecular mechanisms and signalling events after BCR activation. Stable isotope labelling of amino acids in cell culture (SILAC) in combination with mass spectrometry analysis enabled the identification of specific CD22 interaction partners in a quantitative proteomics approach. Hereby, several new CD22 associated proteins were identified that have not been linked to CD22 yet. One of those interacting proteins is cullin 3, an E3 ubiquitin ligase. It was revealed that cullin 3 is important for clathrin-dependent CD22 internalization after BCR stimulation and CD22 surface expression. Further analysis of B-cell specific cullin 3 deficient mice showed an important role of cullin 3 in B cell development. These mice have strongly reduced numbers of mature B cells in the periphery, which are characterized by increased CD22 expression and additionally by pre-activated and apoptotic phenotypes.
2020-05-06 | PXD013801 | Pride
Project description:Expression data comparing the effect of soluble CD22 in monocyte-derived microlgia and in mouse. Expression data on the effect of SM03 in Aβ-injected AD model in human CD22 transgenic mice.
2024-06-10 | GSE269121 | GEO
Project description:Rattus norvegicus Cd22, CD22 molecule [Source:RGD Symbol;Acc:1311610], is expressed in 4 baseline experiment(s);
| ENSRNOG00000024000 | ExpressionAtlas
Project description:Rattus norvegicus Cd22, CD22 molecule [Source:RGD Symbol;Acc:1311610], is differentially expressed in 22 experiment(s);
| ENSRNOG00000024000 | ExpressionAtlas
Project description:Chimeric antigen receptor (CAR) T cells are effective against B-cell malignancies but are associated with cytokine-driven inflammatory toxicities such as cytokine release syndrome (CRS). Historically, T cell receptor (TCR) engineered T cell therapies are rarely associated with CRS. However, it is challenging to compare diverse cell products utilized in different clinical contexts and against different antigens. In this study, TCR and CAR were made to target the same source of antigen, CD22, expressed by B-cell malignancies: the TCR recognizes CD22-derived peptide processed and presented in the context of HLA-A*02:01, and the CAR recognizes CD22 protein expressed on the cell surface. In vivo studies comparing the CD22 TCR-T cells to CD22 CAR-T cells demonstrated that the TCR-T cells could clear leukemia without inducing systemic proinflammatory cytokine elevation, whereas CD22 CAR-T cells induced high levels of circulating proinflammatory cytokine reminiscent of CRS. T cells activated through either the TCR or CAR by an identical leukemia cell line demonstrated differential transcriptional responses. T cells activated via the CAR had disproportionate and significant upregulation of inflammatory gene sets compared to T-cells activated via the TCR.
2025-04-16 | GSE255323 | GEO
Project description:Sus scrofa CD22, CD22 molecule [Source:VGNC Symbol;Acc:VGNC:86398], is differentially expressed in 1 experiment(s);
| ENSSSCG00000002893 | ExpressionAtlas
Project description:Sus scrofa CD22, CD22 molecule [Source:VGNC Symbol;Acc:VGNC:86398], is expressed in 1 baseline experiment(s);
| ENSSSCG00000002893 | ExpressionAtlas
Project description:Homo sapiens CD22, CD22 molecule [Source:HGNC Symbol;Acc:HGNC:1643], is differentially expressed in 106 experiment(s);
| ENSG00000012124 | ExpressionAtlas