Browse
Submit Data
Databases
API
Help

Dataset Information

5 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Human Fc?RII (CD32) Family of Leukocyte FcR in Health and Disease.

ABSTRACT: Fc?Rs have been the focus of extensive research due to their key role linking innate and humoral immunity and their implication in both inflammatory and infectious disease. Within the human Fc?R family Fc?RII (activatory Fc?RIIa and Fc?RIIc, and inhibitory Fc?RIIb) are unique in their ability to signal independent of the common ? chain. Through improved understanding of the structure of these receptors and how this affects their function we may be able to better understand how to target Fc?R specific immune activation or inhibition, which will facilitate in the development of therapeutic monoclonal antibodies in patients where Fc?RII activity may be desirable for efficacy. This review is focused on roles of the human Fc?RII family members and their link to immunoregulation in healthy individuals and infection, autoimmunity and cancer.

SUBMITTER: Anania JC

PROVIDER: S-EPMC6433993 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The Human FcγRII (CD32) Family of Leukocyte FcR in Health and Disease.

Anania Jessica C JC Chenoweth Alicia M AM Wines Bruce D BD Hogarth P Mark PM

Frontiers in immunology 20190319

FcγRs have been the focus of extensive research due to their key role linking innate and humoral immunity and their implication in both inflammatory and infectious disease. Within the human FcγR family FcγRII (activatory FcγRIIa and FcγRIIc, and inhibitory FcγRIIb) are unique in their ability to signal independent of the common γ chain. Through improved understanding of the structure of these receptors and how this affects their function we may be able to better understand how to target FcγR spe ...[more]

PMID: 30941127

Similar Datasets

Human FcR polymorphism and disease.

Project description:Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical FcγRs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture.

| S-EPMC4209745 | biostudies-literature

Human Liver Macrophage Subsets Defined by CD32.

Project description:Human liver myeloid cells are imperfectly defined, but it is broadly agreed that cells of stellate appearance in situ, expressing the markers CD11b and CD68, are the liver's resident macrophages, classically termed Kupffer cells. Recent investigations using single cell RNA sequencing and unsupervised clustering algorithms suggest there are two populations of cells with the characteristics of tissue macrophages in human liver. We therefore analyzed dissociated human liver tissue using the markers CD11b and CD68 to define macrophage-like cells and found within this population two subsets that differ in their expression of multiple surface markers. These subsets were FACS-sorted based on CD32 expression, and gene expression analysis identified them with human liver myeloid cell subsets that were previously defined by two independent single cell RNA sequencing studies. Using qRT-PCR we found that the two subsets differed in the expression of genes associated with T cell activation and immunosuppression, suggesting distinct roles in T cell tolerance. In addition, one subset expressed two markers, CD1C and CD11c, more often seen on classical dendritic cells. Criteria used to distinguish macrophages from dendritic cells in other tissues may need to be revised in the human liver.

| S-EPMC7546764 | biostudies-literature

FCR

Project description:Host Transcriptomics and gut microbiome analysis in broilers with contrasting Feed Conversion Ratio (FCR).

| PRJEB20199 | ENA

Human leukocyte antigen variation and Parkinson's disease.

Project description:A role for the immune system in the pathogenesis of Parkinson's Disease (PD) has previously been suggested. A recent genome-wide association (GWA) study identified an association between one single nucleotide polymorphism (SNP) in the human leucocyte antigen (HLA) region (HLA-DRA rs3129882) and PD in a population of American patients with European ancestry. In that study, the minor rs3129882 allele (G) was associated with an increased risk of PD under an additive model. Due to the increased likelihood of obtaining false positive results in GWA studies compared to studies conducted based on a hypothesis-driven approach, repeated validation of findings from GWA studies are necessary. Herein, we evaluated the association between rs3129882 and PD in three different Caucasian patient-control series (combined 1313 patients and 1305 controls) from the US, Ireland, and Poland. We observed no association (OR: 0.96, P = 0.50) between rs3129882 and PD when analyzing our data under an additive or dominant model. In contrast, when examined under a recessive model, the GG genotype was observed to be protective in the Irish (OR: 0.55, P = 0.008), Polish (OR: 0.67, P = 0.040) and combined (OR: 0.75, P = 0.006) patient-control series. In view of these diverging results, the exact role of genetic variation at the HLA region and susceptibility to PD remains to be resolved.

| S-EPMC3109190 | biostudies-literature

The Xenopus FcR family demonstrates continually high diversification of paired receptors in vertebrate evolution.

Project description:BackgroundRecent studies have revealed an unexpected diversity of domain architecture among FcR-like receptors that presumably fulfill regulatory functions in the immune system. Different species of mammals, as well as chicken and catfish have been found to possess strikingly different sets of these receptors. To better understand the evolutionary history of paired receptors, we extended the study of FcR-like genes in amphibian representatives Xenopus tropicalis and Xenopus laevis.ResultsThe diploid genome of X. tropicalis contains at least 75 genes encoding paired FcR-related receptors designated XFLs. The allotetraploid X. laevis displays many similar genes primarily expressed in lymphoid tissues. Up to 35 domain architectures generated by combinatorial joining of six Ig-domain subtypes and two subtypes of the transmembrane regions were found in XFLs. None of these variants are shared by FcR-related proteins from other studied species. Putative activating XFLs associate with the FcRgamma subunit, and their transmembrane domains are highly similar to those of activating mammalian KIR-related receptors. This argues in favor of a common origin for the FcR and the KIR families. Phylogenetic analysis shows that the entire repertoires of the Xenopus and mammalian FcR-related proteins have emerged after the amphibian-amniotes split.ConclusionFcR- and KIR-related receptors evolved through continual species-specific diversification, most likely by extensive domain shuffling and birth-and-death processes. This mode of evolution raises the possibility that the ancestral function of these paired receptors was a direct interaction with pathogens and that many physiological functions found in the mammalian receptors were secondary acquisitions or specializations.

| S-EPMC2413239 | biostudies-literature

Human Kupffer Cell Subsets Defined by CD32

Project description:Human liver myeloid cells are imperfectly defined, but it is broadly agreed that cells of stellate appearance in situ, expressing the markers CD11b and CD68, are the liver’s resident macrophages, termed Kupffer cells. Recent investigations using single cell RNA sequencing and unsupervised clustering algorithms suggest there are two populations of cells with the characteristics of tissue macrophages in human liver. We therefore analyzed dissociated human liver tissue using the markers CD11b and CD68 to define Kupffer cells and found within this population two subsets that differ in their expression of multiple surface markers. These subsets were FACS-sorted based on CD32 expression, and gene expression analysis identified them with human liver myeloid cell subsets defined by two independent single cell RNA sequencing studies. These two subsets differed in the expression of genes associated with T cell activation and immunosuppression, suggesting distinct roles in T cell tolerance.

2020-10-27 | GSE154318 | GEO

Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9.

Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies against nucleoproteins and DNA. Here we show that DNA-containing immune complexes (ICs) within lupus serum (SLE-ICs), but not protein-containing ICs from other autoimmune rheumatic diseases, stimulates plasmacytoid DCs (PDCs) to produce cytokines and chemokines via a cooperative interaction between Toll-like receptor 9 (TLR9) and FcgammaRIIa (CD32). SLE-ICs transiently colocalized to a subcellular compartment containing CD32 and TLR9, and CD32+, but not CD32-, PDCs internalized and responded to SLE-ICs. Our findings demonstrate a novel functional interaction between Fc receptors and TLRs, defining a pathway in which CD32 delivers SLE-ICs to intracellular lysosomes containing TLR9, inducing a signaling cascade leading to PDC activation. These data demonstrate that endogenous DNA-containing autoantibody complexes found in the serum of patients with SLE activate the innate immune system and suggest a novel mechanism whereby these ICs contribute to the pathogenesis of this autoimmune disease.

| S-EPMC544604 | biostudies-literature

Leukocyte mono-immunoglobulin-like receptor 8 (LMIR8)/CLM-6 is an FcR?-coupled receptor selectively expressed in mouse tissue plasmacytoid dendritic cells.

Project description:Plasmacytoid dendritic cells (pDCs) produce large amounts of type-I interferon (IFN) in response to viral infection or self nucleic acids. Leukocyte mono-immunoglobulin-like receptor 8 (LMIR8), also called CMRF-35-like molecule-6 (CLM-6), is a putative activating receptor among mouse LMIR/CLM/CD300 members; however, the expression and function of LMIR8 remain unclear. Here, we characterize mouse LMIR8 as a pDC receptor. Analysis of Flag-tagged LMIR8-transduced bone marrow (BM)-derived mast cells demonstrated that LMIR8 can transmit an activating signal by interacting with immunoreceptor tyrosine-based activating motif (ITAM)-containing FcR?. Flow cytometric analysis using a specific antibody for LMIR8 showed that LMIR8 expression was restricted to mouse pDCs residing in BM, spleen, or lymph node. FcR? deficiency dampened surface expression of LMIR8 in mouse pDCs. Notably, LMIR8 was detected only in pDCs, irrespective of TLR9 stimulation, suggesting that LMIR8 is a suitable marker for pDCs in mouse tissues; LMIR8 is weakly expressed in Flt3 ligand-induced BM-derived pDCs (BMpDCs). Crosslinking of transduced LMIR8 in BMpDCs with anti-LMIR8 antibody did not induce IFN-? production, but rather suppressed TLR9-mediated production of IFN-?. Taken together, these observations indicate that LMIR8 is an FcR?-coupled receptor selectively expressed in mouse tissue pDCs, which might suppress pDC activation through the recognition of its ligands.

| S-EPMC5974347 | biostudies-literature

A novel family of human leukocyte antigen class II receptors may have its origin in archaic human species.

Project description:HLA class II ? and ? chains form receptors for antigen presentation to CD4(+) T cells. Numerous pairings of class II ? and ? subunits from the wide range of haplotypes and isotypes may form, but most of these combinations, in particular those produced by isotype mixing, yielded mismatched dimers. It is unclear how selection of functional receptors is achieved. At the atomic level, it is not known which interactions of class II residues regulate selection of matched ?? heterodimers and the evolutionary origin of matched isotype mixed dimer formation. In this study we investigated assembly of isotype-mixed HLA class II ? and ? heterodimers. Assembly and carbohydrate maturation of various HLA-class II isotype-mixed ? and ? subunits was dependent on the groove binding section of the invariant chain (Ii). By mutation of polymorphic DP? sequences, we identified two motifs, Lys-69 and GGPM-(84-87), that are engaged in Ii-dependent assembly of DP? with DR?. We identified five members of a family of DP? chains containing Lys-69 and GGPM 84-87, which assemble with DR?. The Lys/GGPM motif is present in the DP? sequence of the Neanderthal genome, and this ancient sequence is related to the human allele DPB1*0401. By site-directed mutagenesis, we inspected Neanderthal amino acid residues that differ from the DPB1*0401 allele and aimed to determine whether matched heterodimers are formed by assembly of DP? mutants with DR?. Because the *0401 allele is rare in the sub-Saharan population but frequent in the European population, it may have arisen in modern humans by admixture with Neanderthals in Europe.

| S-EPMC3887193 | biostudies-literature

IL-3 up-regulates and activates human eosinophil CD32 and αMβ2 integrin causing degranulation.

Project description:BackgroundEosinophils contribute to the pathogenesis of multiple diseases, including asthma. Treatment with antibodies targeting IL-5 or IL-5 receptor α reduces the frequency of asthma exacerbations. Eosinophil receptors for IL-5 share a common ß-chain with IL-3 and GM-CSF receptors. We recently reported that IL-3 is more potent than IL-5 or GM-CSF in maintaining the ERK/p90S6K/RPS6 ribosome-directed signaling pathway, leading to increased protein translation.ObjectiveWe aimed to determine disease-relevant consequences of prolonged eosinophil stimulation with IL-3.ResultsHuman blood eosinophils were used to establish the impact of activation with IL-3 on IgG-driven eosinophil degranulation. When compared to IL-5, continuing exposure to IL-3 further induced degranulation of eosinophils on aggregated IgG via increased production and activation of both CD32 (low affinity IgG receptor) and αMß2 integrin. In addition, unlike IL-5 or GM-CSF, IL-3 induced expression of CD32B/C (FCGRIIB/C) subtype proteins, without changing CD32A (FCGRIIA) protein and CD32B/C mRNA expression levels. Importantly, these in vitro IL-3-induced modifications were recapitulated in vivo on airway eosinophils.Conclusions and clinical relevanceWe observed for the first time upregulation of CD32B/C on eosinophils, and identified IL-3 as a potent inducer of CD32- and αMß2-mediated eosinophil degranulation.

| S-EPMC5378663 | 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