Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A small CD11b(+) human B1 cell subpopulation stimulates T cells and is expanded in lupus.

ABSTRACT: A primary function of B lymphocytes is immunoglobulin production; however, the therapeutic benefit of B cell depletion in autoimmune diseases previously thought to be T cell mediated suggests that some B cells fulfill other roles in autoimmunity. We examined the recently identified human B1 cell population for T cell stimulatory activity. We found two kinds of B1 cells that are distinguished by multiple surface markers and distinct transcriptomic profiles. In both umbilical cord and adult peripheral blood, a CD11b(+) subset constitutes ~1 out of every 8-10 B1 cells, whereas a CD11b(-) subset constitutes the remaining B1 cells. These B1 cell populations differ functionally. CD11b(-) B1 cells spontaneously secrete much more IgM than CD11b(+) B1 cells. In contrast, CD11b(+) B1 cells express more CD86, and more efficiently stimulate allogeneic CD4(+) T cell expansion, than CD11b(-) B1 cells. The frequency of these CD11b(+) B1 cells is markedly elevated in lupus patients. CD11b(+) B1 cells in lupus patients express more CD86 and have increased T cell-stimulating activity in disease. This work distinguishes a novel, T cell-interacting B1 cell population whose abundance and activity may be a reflection of, and a therapeutic target in, autoimmune disease.

SUBMITTER: Griffin DO

PROVIDER: S-EPMC3244038 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Gene profiling of CD11b⁺ and CD11b⁻ B1 cell subsets reveals potential cell sorting artifacts.

Project description: Not available

| S-EPMC3302223 | biostudies-literature

CD11b Activity Modulates Pathogenesis of Lupus Nephritis.

Project description:Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) with unclear etiology and limited treatment options. Immune cell infiltration into the kidneys, a hallmark of LN, triggers tissue damage and proteinuria. CD11b, the α-chain of integrin receptor CD11b/CD18 (also known as αMβ2, Mac-1, and CR3), is highly expressed on the surface of innate immune cells, including macrophages and neutrophils. Genetic variants in the human ITGAM gene, which encodes for CD11b, are strongly associated with susceptibility to SLE, LN, and other complications of SLE. CD11b modulates several key biological functions in innate immune cells, including cell adhesion, migration, and phagocytosis. CD11b also modulates other signaling pathways in these cells, such as the Toll-like receptor signaling pathways, that mediate generation of type I interferons, a key proinflammatory cytokine and circulating biomarker in SLE and LN patients. However, how variants in ITGAM gene contribute to disease pathogenesis has not been completely established. Here, we provide an overview of CD11b modulated mechanisms and the functional consequences of the genetic variants that can drive disease pathogenesis. We also present recent insights from studies after pharmacological activation of CD11b. These studies offer novel mechanisms for development of therapeutics for LN, SLE and other autoimmune diseases.

| S-EPMC5862812 | biostudies-literature

CD44+/EPCAM+ cells detect a subpopulation of ALDHhigh cells in human non-small cell lung cancer: A chance for targeting cancer stem cells?

Project description:OBJECTIVES:Several studies demonstrated that aldehyde dehydrogenase (ALDH) and CD44 are the most considered cancer stem cells (CSC) markers. However, a comparison between ALDH high cells and CD44+ cells have been previously described with no significant correlation. Indeed, the aim of the present research is to identify a superficial marker able to match with ALDH high cells population in freshly isolated human lung cancer cells. MATERIALS AND METHODS:This cross-sectional study analyzed the expression of ALDHhigh/low cells and the positivity for CD44 and epithelium cell adhesion molecule (EPCAM) antigens in surgical lung cancer tissues. The main approach was a cytofluorimetric analysis of ALDH expression and positivity for CD44/EPCAM on primary cell population obtained from 23 patients harboring NSCLC. RESULTS:There was a highly positive correlation between the expressions of ALDHhigh and CD44+/EPCAM+ cells, with a Pearson's correlation coefficient equal to 0.69 (95% CI 0.39-0.86; P = 0.0002), and Spearman's correlation coefficient equal to 0.52 (P = 0.0124). The average paired difference between the expression of ALDHhigh and CD44+/EPCAM+ cells was very close to 0, being 0.1% (SD 2.5%); there was no difference between these subpopulations in terms of means (95% CI = -1.0; 1.2%, P = 0.8464). These results highlight a strong similarity between ALDHhigh and CD44+/EPCAM+ cells. CONCLUSIONS:Our study is the first attempt which identifies a high correlation between the ALDHhigh and the CD44+/EPCAM+ cells, thus suggesting the possibility to use this superficial marker for future target treatments against lung cancer stem cells.

| S-EPMC7197447 | biostudies-literature

Phagocytosis is the main CR3-mediated function affected by the lupus-associated variant of CD11b in human myeloid cells.

Project description:The CD11b/CD18 integrin (complement receptor 3, CR3) is a surface receptor on monocytes, neutrophils, macrophages and dendritic cells that plays a crucial role in several immunological processes including leukocyte extravasation and phagocytosis. The minor allele of a non-synonymous CR3 polymorphism (rs1143679, conversation of arginine to histidine at position 77: R77H) represents one of the strongest genetic risk factor in human systemic lupus erythematosus, with heterozygosity (77R/H) being the most common disease associated genotype. Homozygosity for the 77H allele has been reported to reduce adhesion and phagocytosis in human monocytes and monocyte-derived macrophages, respectively, without affecting surface expression of CD11b. Herein we comprehensively assessed the influence of R77H on different CR3-mediated activities in monocytes, neutrophils, macrophages and dendritic cells. R77H did not alter surface expression of CD11b including its active form in any of these cell types. Using two different iC3b-coated targets we found that the uptake by heterozygous 77R/H macrophages, monocytes and neutrophils was significantly reduced compared to 77R/R cells. Allele-specific transduced immortalized macrophage cell lines demonstrated that the minor allele, 77H, was responsible for the impaired phagocytosis. R77H did not affect neutrophil adhesion, neutrophil transmigration in vivo or Toll-like receptor 7/8-mediated cytokine release by monocytes or dendritic cells with or without CR3 pre-engagement by iC3b-coated targets. Our findings demonstrate that the reduction in CR3-mediated phagocytosis associated with the 77H CD11b variant is not macrophage-restricted but demonstrable in other CR3-expressing professional phagocytic cells. The association between 77H and susceptibility to systemic lupus erythematosus most likely relates to impaired waste disposal, a key component of lupus pathogenesis.

| S-EPMC3579793 | biostudies-literature

Subpopulation of small-cell lung cancer cells expressing CD133 and CD87 show resistance to chemotherapy.

Project description:Tumors are presumed to contain a small population of cancer stem cells (CSCs) that initiate tumor growth and promote tumor spreading. Multidrug resistance in CSCs is thought to allow the tumor to evade conventional therapy. This study focused on expression of CD133 and CD87 because CD133 is a putative marker of CSCs in some cancers including lung, and CD87 is associated with a stem-cell-like property in small-cell lung cancer (SCLC). Six SCLC cell lines were used. The expression levels of CD133 and CD87 were analyzed by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry. CD133+/- and CD87+/- cells were isolated by flow cytometry. The drug sensitivities were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-obese diabetic/severe combined immunodeficiency mice were used for the tumor formation assay. SBC-7 cells showed the highest expression levels of both CD133 and CD87 among the cell lines. CD133-/CD87-, CD133+/CD87-, and CD133-/CD87+ cells were isolated from SBC-7 cells; however, CD133+/CD87+ cells could not be obtained. Both CD133+/CD87- and CD133-/CD87+ subpopulations showed a higher resistance to etoposide and paclitaxel and greater re-populating ability than the CD133-/CD87- subpopulation. CD133+/CD87- cells contained more G0 quiescent cells than CD133-/CD87- cells. By contrast, CD133-/CD87- cells showed the highest tumorigenic potential. In conclusion, both CD133 and CD87 proved to be inadequate markers for CSCs; however, they might be beneficial for predicting resistance to chemotherapy.

| S-EPMC7657141 | biostudies-literature

Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration.

Project description:Aflatoxin B1 (AFB1) is a potent carcinogen that can induce hepatocellular carcinoma. AFB1-8,9-exo-epoxide, one of AFB1 metabolites, acts as a mutagen to react with DNA and induce gene mutations, including the tumor suppressor p53. In addition, AFB1 reportedly stimulates IGF receptor activation. Aberrant activation of IGF-I receptor (IGF-IR) signaling is tightly associated with various types of human tumors. In the current study, we investigated the effects of AFB1 on key elements in IGF-IR signaling pathway, and the effects of AFB1 on hepatoma cell migration. The results demonstrated that AFB1 induced IGF-IR, Akt, and Erk1/2 phosphorylation in hepatoma cell lines HepG2 and SMMC-7721, and an immortalized human liver cell line Chang liver. AFB1 also down-regulated insulin receptor substrate (IRS) 1 but paradoxically up-regulated IRS2 through preventing proteasomal degradation. Treatment of hepatoma cells and Chang liver cells with IGF-IR inhibitor abrogated AFB1-induced Akt and Erk1/2 phosphorylation. In addition, IRS2 knockdown suppressed AFB1-induced Akt and Erk1/2 phosphorylation. Finally, AFB1 stimulated hepatoma cell migration. IGF-IR inhibitor or IRS2 knockdown suppressed AFB1-induced hepatoma cell migration. These data demonstrate that AFB1 stimulates hepatoma cell migration through IGF-IR/IRS2 axis.

| S-EPMC3480444 | biostudies-literature

Single-Cell Transcriptome Analysis of Human Adipose-Derived Stromal Cells Identifies a Contractile Cell Subpopulation.

Project description:The potential for human adipose-derived stromal cells (hASCs) to be used as a therapeutic product is being assessed in multiple clinical trials. However, much is still to be learned about these cells before they can be used with confidence in the clinical setting. An inherent characteristic of hASCs that is not well understood is their heterogeneity. The aim of this exploratory study was to characterize the heterogeneity of freshly isolated hASCs after two population doublings (P2) using single-cell transcriptome analysis. A minimum of two subpopulations were identified at P2. A major subpopulation was identified as contractile cells which, based on gene expression patterns, are likely to be pericytes and/or vascular smooth muscle cells (vSMCs).

| S-EPMC8102097 | biostudies-literature

A distinct subpopulation of human NK cells restricts B cell transformation by EBV.

Project description:NK cells constitute the first line of defense against pathogens and transformed cells. They mature in secondary lymphoid organs, including tonsils, where common pathogens, such as EBV, enter the host and potentially imprint differentiating cells, which then patrol the body via the blood stream. Therefore, we set out to characterize a distinct human NK cell population in tonsils that produces high amounts of the immunomodulatory and antiviral cytokine IFN-γ. We found that the tonsilar IFN-γ(high) NK cell subset is CD56(bright)NKG2A(+)CD94(+)CD54(+)CD62L(-), is present in tonsils ex vivo and is more mature than other CD56(bright) NK cells in tonsils and less mature than other NK cells in blood, shows very low plasticity even after prolonged cytokine stimulation, accumulates in tonsils of EBV carriers, and is able to potently restrict EBV-induced transformation of B cells. Thus, we characterized a distinct and stable IFN-γ(high) NK cell subpopulation that can specifically restrict malignant transformation of EBV-infected B cells. This subset should be exploited for future development of cell-based therapeutic approaches in EBV-associated malignancies.

| S-EPMC3833632 | biostudies-literature

CD11b agonists offer a novel approach for treating lupus nephritis.

Project description:Lupus nephritis (LN) develops in more than a third of all systemic lupus erythematosus (SLE) patients and is the strongest predictor of morbidity and mortality. Increased circulating levels of type I interferon (IFN I) and anti-double stranded DNA (anti-dsDNA) and anti-RNA binding protein (anti-RNP) antibodies lead to increased glomerular injury via leukocyte activation and glomerular infiltration. Uncontrolled Toll-like receptor (TLR) signaling in leukocytes results in increased production of IFN I and anti-dsDNA antibodies. ITGAM gene codes for integrin CD11b, the α-chain of integrin heterodimer CD11b/CD18, that is highly expressed in leukocytes and modulates TLR-dependent pro-inflammatory signaling. Three nonsynonymous SNPs in the ITGAM gene strongly correlate with increased risk for SLE and LN and with IFN I levels. Here we review the literature on the role of CD11b on leukocytes in LN. We also incorporate conclusions from several recent studies that show that these ITGAM SNPs result in a CD11b protein that is less able to suppress TLR-dependent pro-inflammatory pathways in leukocytes, that activation of CD11b via novel small molecule agonists suppresses TLR-dependent pathways, including reductions in circulating levels of IFN I and anti-dsDNA antibodies, and that CD11b activation reduces LN in model systems. Recent data strongly suggest that integrin CD11b is an exciting new therapeutic target in SLE and LN and that allosteric activation of CD11b is a novel therapeutic paradigm for effectively treating such autoimmune diseases.

| S-EPMC9167730 | biostudies-literature

A Novel Type I Interferon Primed Dendritic Cell Subpopulation in TREX1 Mutant Chilblain Lupus Patients

Project description:Heterozygous TREX1 mutations are associated with monogenic familial chilblain lupus and represent a risk factor for developing systemic lupus erythematosus. These interferonopathies originate from chronic type I interferon stimulation due to sensing of inadequately accumulating nucleic acids. We here analysed the composition of dendritic cell (DC) subsets, central stimulators of immune responses, in patients with TREX1 deficiency. We performed single-cell RNA-sequencing of peripheral blood DCs and monocytes from two patients with familial chilblain lupus and heterozygous mutations in TREX1 and from controls. Type I interferon pathway genes were strongly upregulated in patients. Cell frequencies of the myeloid and plasmacytoid DC and of monocyte populations in patients and controls were similar, but we describe a novel DC subpopulation highly enriched in patients: a myeloid DC CD1C+ subpopulation characterized by the expression of LMNA, EMP1 and a type I interferon- stimulated gene profile. The presence of this defined subpopulation was confirmed in a second cohort of patients and controls by flow cytometry, also revealing that an increased percentage of patient’s cells in the subcluster express costimulatory molecules. We identified a novel type I interferon responsive myeloid DC subpopulation, that might be important for the perpetuation of TREX1-induced chilblain lupus and other type I interferonopathies.

| S-EPMC9327789 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data