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IL-4 induces CD22 expression to restrain the effector program of self-reactive virtual memory T cells

ABSTRACT: IL-4 induces CD22 expression to restrain the effector program of self-reactive virtual memory T cells

PROVIDER: PRJNA950375 | ENA |

REPOSITORIES: ENA

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IL-4 induces CD22 expression to restrain the effector program of self-reactive virtual memory T cells

Project description:Parasitic helminths induce the production of interleukin (IL)-4 which causes the expansion of virtual memory CD8+ T cells (TVM), a cell subset contributing to the control of viral coinfection. However, the mechanisms regulating IL-4-dependent TVM activation and expansion during worm infection remain ill defined. We used single-cell RNA sequencing of CD8+ T cells to investigate IL-4-dependent TVM responses upon helminth infection in mice. Gene signature analysis of CD8+ T cells identified a cell cluster marked by CD22, a canonical regulator of B cell activation, as a specific and selective surface marker of IL-4-induced TVM cells. CD22+ TVM were enriched for IFN-γ and granzyme A and retained a diverse TCR repertoire, while enriched in CDR3 sequences with features of self-reactivity. Deletion of CD22 expression in CD8+ T cells enhanced TVM responses to helminth infection, indicating that this inhibitory receptor modulates TVM responses. Thus, helminth-induced IL-4 drives the expansion and activation of self-reactive TVM in the periphery that is counter-inhibited by CD22

2025-01-23 | GSE228564 | GEO

Generation of virtual memory from relatively highly self-reactive is a mechanism of self-tolerance

Project description:Virtual memory T cell show an intermediate expression profile in between naïve and true memory T cells. Most plausible explanation is that they trigger partial memory differentiation program.

2017-11-09 | GSE90522 | GEO

CD22 interactome

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

CD22 modulation regulates neuroinflammation in microglia

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

Sphingomonas sp. CD22

Project description:Sphingomonas sp. CD22 Genome sequencing and assembly

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Clostridioides difficile CD22

Project description:Clostridioides difficile CD22 Genome sequencing and assembly

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Expression data of human CD19pos B lymphocytes (B) and CD19negCD22neg non-B cells (ENV) from non tumoral reactive lymph nodes (RLN), tonsils (TONS) or follicular lymphoma (FL)

Project description:GEP on Affymetrix U133+2.0 microarrays was performed on ex vivo CD19+ B lymphocytes or CD19-CD22- fractions from reactive or FL lymph nodes or normal tonsils.

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Transcriptome analysis of mouse WT and CD22 KO GC B cells

Project description:Germinal centres (GC) are specialized sites where B cells expand and diversify their antibody genes through somatic hypermutation. GC B-cells are routinely identified through distinct changes on their surface carbohydrates, known as glycans. One striking modification relates to the monosaccharide sialic acid. In mice, this change is mediated through downregulation of an enzyme called CMAH, which results in a GC-specific loss of preferred ligand for CD22, a member of the sialic acid-binding immunoglobulin-type lectins (Siglecs) and an inhibitory co-receptor of the B-cell antigen receptor (BCR). Here, we identified that glycan remodeling, mediated by downregulation of CMAH, is crucial for the GC B-cell response, and production of memory B-cells, plasma cells, and high affinity antibodies. We also demonstrated that the function of these altered glycans is dependent on CD22, highlighting that coordinated loss of preferred ligands acts to modulates the CD22 activity in the GC B-cells. Overall, our study reveals that intrinsic glycan remodeling functions to optimize the B-cell responses in the GC by controlling CD22.

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CD22 blockage restores age-related impairments of microglia surveillance capacity

Project description:We report that antibody-mediated CD22 blockage leads to an altered transcriptomic signature profile which, by further evaluating the affected genes, resembles a homeostatic phenotype.

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Project description:Transcriptomics analysis of virtual memory CD8+ T cells after treatment with Schistosoma mansoni eggs.

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