Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An inflammatory loop established between spleen-derived myeloid cells and CD4+ T cells leads to accumulation of long-lived plasma cells that exacerbate lupus autoimmunity

ABSTRACT: Splenic long-lived plasma cells (PCs) are abnormally numerous and deleterious in systemic autoimmune diseases, yet how they accumulate remains poorly understood. We demonstrate here that a pathological role of spleen-derived CD11b+Gr-1+ myeloid cells (SPMCs) underpins the accumulation of splenic long-lived PCs in a lupus-prone model. SPMCs were a mixture of granulocytic and monocytic myeloid-derived suppressor cells (MDSCs) that were expanded and acquired proinflammatory phenotypes in situ during lupus progression. By promoting the development of IFN--secreting and follicular helper T cells, SPMCs licensed CD4+ T cells to be pathologic activators of SPMCs and PCs. SPMCs also directly promoted the survival of PCs by providing B-cell activating factor of the TNF family. The frequency of SPMCs correlated with that of splenic long-lived PCs. Depletion of CD11b+Gr-1+ cells reduced autoantibody production. Thus, our findings suggest that SPMCs expanded in situ establish a positive feedback loop with CD4+ T cells, leading to accumulation of long-lived PCs which exacerbate lupus autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE161850 | GEO | 2021/02/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BAFF and CD4+ T cells are major survival factors for long-lived splenic plasma cells in a B-cell–depletion context

Project description:Previous data have suggested that B-cell–depletion therapy may induce the settlement of autoreactive long-lived plasma cells (LLPCs) in the spleen of patients with autoimmune cytopenia. To investigate this process, we used the AID-CreERT2-EYFP mouse model to follow PCs engaged in an immune response. Multiplex-PCR at the single-cell level revealed that only a small fraction of splenic PCs had a long-lived signature, whereas PCs present after anti-CD20 antibody treatment appeared more mature, similar to bone-marrow PCs. It suggested that, in addition to a process of selection, a maturation induced upon B-cell depletion drove PCs toward a long-lived program. We showed that BAFF and CD4+ T cells play a major role in PC survival niche, because combining anti-CD20 with anti-BAFF or anti-CD4 antibody greatly reduce the number of splenic PCs. Similar results were obtained in the lupus-prone NZB/W model. These different contributions of soluble and cellular components of the PC niche in the spleen demonstrate that the LLPC expression profile is not cell-intrinsic but largely depends on signals provided by the splenic microenvironment, implying that interfering with these components at the time of B cell depletion might improve the response rate in autoimmune cytopenia.

2018-02-19 | E-MTAB-6449 | biostudies-arrayexpress

cDNA microarray analysis of splenic B220+CD138+ plasma cells from K/BxNsf and K/BxN mice

Project description:Long-lived plasma cells (LLPCs) develop under the help of follicular helper T (Tfh) cells and reside mainly in the bone marrow. However, these cells are unusually abundant in the spleen of several autoimmune models including K/BxNsf mice, yet their pathogenic impact remains unknown. To investigate a previously unappreciated role of splenic LLPCs, we sorted splenic plasma cells (PCs) from K/BxNsf and K/BxN mice, corresponding to LLPCs and conventional short-lived PCs, respectively, and compared their transcriptomes. The B220+CD138+ fraction from K/BxNsf and their control K/BxN mice were sorted by FACSariaIII.

2016-03-01 | E-GEOD-66947 | biostudies-arrayexpress

cDNA microarray analysis of splenic B220+CD138+ plasma cells from K/BxNsf and K/BxN mice

2016-03-01 | GSE66947 | GEO

Mus musculus

Project description:Microarray analysis of splenic CD11b+Gr-1+ cells

| PRJNA321034 | ENA

Age-Associated B Cells are Heterogenous and Dynamic in Autoimmunity

Project description:Age-Associated B Cells (ABCs) are a population of CD11c+ and/or CD11b+ B cells expanded in autoimmune lupus. To understand potential heterogeneity within ABCs and the relationship of ABCs to other splenic B cell subsets, we performed scRNA-seq with 5' V(D)J and CITE-seq cell surface features using the 10x Genomics Chromium platform on total splenic CD19+ B cells sorted from lupus-prone MRL/lpr. We found that ABC are a distinct transcriptional lineage that resolved into two related clusters. Analysis of BCR heavy chains identified clones present in both ABC and plasmablast compartments. Inferred lineage trees based on V gene somatic hypermutation suggested that self-renewing ABC feed into the plasmablast compartment repeatedly while continuing to themselves undergo mutation and expansion.

2023-01-01 | GSE202110 | GEO

Immunomolecular and reactivity landscapes of gut IgA subclasses in homeostasis and inflammatory bowel diseases.

Project description:The human gut includes plasma cells (PCs) expressing immunoglobulin A1 (IgA1) or IgA2, two structurally distinct IgA subclasses with elusive regulation, function and reactivity. We show here that intestinal IgA1+ and IgA2+ PCs co-emerged early in life, comparably accumulated somatic mutations, and were enriched within short-lived CD19+ and long-lived CD19− PC subsets, respectively. IgA2+ PCs were often clonally related to IgA1+ PCs and a subset of them presumably emerged from IgA1+ precursors. Of note, secretory IgA1 (SIgA1) and SIgA2 dually coated a large fraction of mucus-embedded bacteria, including Akkermansia muciniphila. Disruption of homeostasis by inflammatory bowel disease (IBD) increased newly formed and actively proliferating IgA1+ plasmablasts, depleted long-lived IgA2+ PCs, and increased SIgA1+SIgA2+ gut microbiota. Such increase featured enhanced IgA1 reactivity to pathobionts, including Escherichia coli, combined with depletion of beneficial Akkermansia muciniphila. Thus, gut IgA1 and IgA2 emerge from clonally related PCs and show unique changes of both frequency and reactivity in IBD.

2024-10-17 | GSE268929 | GEO

Single cell RNA seq reveals cellular and transcriptional heterogeneity in the splenic CD11b+Ly6Chigh monocyte population expanded in sepsis-surviving mice

Project description:Patients surviving a septic episode exhibit persistent immune impairment and increased mortality due to enhanced infection vulnerability. In the present study, using the cecal ligation and puncture (CLP) model of polymicrobial sepsis, we addressed the hypothesis that functional, metabolic, and phenotypic alterations in splenic CD11b+Ly6Chigh myeloid cells contribute to the immune impairment in sepsis-surviving mice. Herein, we showed the cellular and transcriptional heterogeneity of the expanded splenic CD11b+Ly6Chigh population in CLP-survivors. We also showed that CD11b+Ly6Chigh cells presented phenotypic and functional disparity between C57BL6/J and BALB/c strains.

2024-11-13 | GSE249839 | GEO

Single-cell RNA-seq reveals distinct maturation stages of the Paneth cell lineage

Project description:Paneth cells (PCs) are long-lived secretory cells that reside at the bottoms of small intestinal crypts. Besides serving as niche cells for the neighboring Lgr5-positive stem cells, PCs secrete granules containing a broad spectrum of antimicrobial proteins, including lysozymes and defensins1. Here, we have used single-cell RNA sequencing to explore PC differentiation. We found a maturation gradient from early secretory progenitors to mature PCs, capturing the full maturation path of PCs. Moreover, differential expression of a subset of defensin genes in lysozyme-high PCs, e.g. Defa20, reveals at least two distinct stages of maturation. We traced Lgr5+ stem cells from Lgr5-CreERT2 C57Bl6/J mice bred to a Rosa26LSL-YFP reporter mice and sorted YFP+ cells 5 days, 3 weeks and 8 weeks after tamoxifen injection.

2016-06-23 | E-GEOD-76408 | biostudies-arrayexpress

MatthieuMAHEVAS

Project description:Splenic tissues from immune thrombocytopenia purpura (ITP) patients splenectomized after primary failure of treatment with the B-cell depleting agent rituximab were analyzed, and antibody-secreting cells were identified as the major B-cell population resisting the treatment. The phenotype, antibody specificity and gene expression profile of these cells were characterized and compared to antibody-secreting cells from untreated ITP spleens and from healthy tissues. Anti-platelet-specific plasma cells (PC) were detected in the spleen of ITP patients up to 6 months after rituximab treatment, and the PC population displayed a long-lived program similar to the one of bone marrow PC, thus explaining for most of these patients the absence of response to rituximab and the response to splenectomy. When analyzed by multiplex PCR at the singlecell level, normal splenic PC showed a markedly different gene expression profile, with an intermediate signature including genes characteristic of both long-lived PC and proliferating plasmablasts. Surprisingly, long-lived PC were not detected either in the inflammatory environment of the untreated ITP spleen. These results suggest that neither the normal nor the auto-immune splenic environment favors the differentiation and residence of long-lived PC, and that it is most probably the milieu generated by B-cell depletion that promotes their local settlement.

2013-08-08 | E-MEXP-3711 | biostudies-arrayexpress

Single-cell RNA-seq reveals distinct maturation stages of the Paneth cell lineage

2016-06-23 | GSE76408 | GEO