CD25FOXP3CD45RA regulatory T-cell infiltration as a prognostic biomarker for endometrial carcinoma.

Background: Regulatory T (Treg) cells reportedly play crucial roles in tumor angiogenesis as well as antitumor immunity. In order to explore their therapeutic potential, we investigated the precise prognostic impact of Treg markers in endometrial carcinoma.

Methods: We performed multiplexed immunofluorescence and quantitative image analyses of CD25, FOXP3, CTLA4, and CD45RA in tumor specimens from 176 consecutive patients treated at our institution for primary endometrial carcinomas.

Development of Monoclonal Antibodies Specific to Either CD300A or CD300A or Both.

CD300A is a member of the CD300 immunoglobulin (Ig)-like receptor family consisting of eight molecules in humans, all of which contain one Ig-like domain in the extracellular portion. Upon binding its ligand phosphatidylserine or phosphatidylethanolamine, CD300A mediates an inhibitory signal through the immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic portion. The CD300 family molecules are highly homologous to each other.

Protective effects of S100A8 on sepsis mortality: Links to sepsis risk in obesity and diabetes.

Obesity and diabetes are independent risk factors for death during sepsis. S100A8, an alarmin, is related to inflammation, obesity, and diabetes. Here, we examine the role of S100A8 in sepsis of obesity and diabetes models.

Interferon-β promotes the survival and function of induced regulatory T cells.

Type I interferons (IFNs) are pleiotropic cytokines and impact various immune cells, including regulatory T cells (Treg cells). The effect of type-I IFNs on the development and function of Treg cells is quite controversial. Here we induced Treg cells (iTreg cells) from naïve CD4 T cells in vitro in the presence or absence of IFN-β to elucidate its direct effect on the induction of iTreg cells.

Tumor-derived extracellular vesicles regulate tumor-infiltrating regulatory T cells via the inhibitory immunoreceptor CD300a.

Although tumor-infiltrating regulatory T (Treg) cells play a pivotal role in tumor immunity, how Treg cell activation are regulated in tumor microenvironments remains unclear. Here, we found that mice deficient in the inhibitory immunoreceptor CD300a on their dendritic cells (DCs) have increased numbers of Treg cells in tumors and greater tumor growth compared with wild-type mice after transplantation of B16 melanoma. Pharmacological impairment of extracellular vesicle (EV) release decreased Treg cell numbers in CD300a-deficient mice.

CD300a blockade enhances efferocytosis by infiltrating myeloid cells and ameliorates neuronal deficit after ischemic stroke.

Immune responses contribute to tissue injury and repair during and after ischemic stroke. However, the spatiotemporal and initiating molecular events remain incompletely understood. Here, we show that mice deficient in the phosphatidylserine receptor CD300a, which is highly expressed on brain myeloid cells including Ly6C monocytes, exhibited ameliorated neurological deficit after middle cerebral artery occlusion (MCAO).

Cutting Edge: Involvement of the Immunoreceptor CD300c2 on Alveolar Macrophages in Bleomycin-Induced Lung Fibrosis.

Idiopathic pulmonary fibrosis is a chronic, progressive, and irreversible fibrotic lung disease. Although inflammation plays a central role in the pathogenesis of idiopathic pulmonary fibrosis, how inflammatory responses are regulated remains unclear. In this article, we show that mice deficient in the immunoreceptor CD300c2 (also called MAIR-II, LMIR2, and CLM-4) showed longer survival; less collagen deposition in the lung; lower levels of neutrophil chemoattractants, such as TNF-α, CXCL1, and CCL2; and fewer neutrophils in the bronchoalveolar fluid than wild-type mice after intratracheal administration of bleomycin (BLM).

Elovl6 regulates mechanical damage-induced keratinocyte death and skin inflammation.

Mechanical damage on the skin not only affects barrier function but also induces various immune responses, which trigger or exacerbate skin inflammation. However, how mechanical damage-induced skin inflammation is regulated remains incompletely understood. Here, we show that keratinocytes express the long-chain fatty-acid elongase Elovl6.

Identification and isolation of splenic tissue-resident macrophage sub-populations by flow cytometry.

Tissue-resident macrophages in the spleen, including red pulp and white pulp macrophages, marginal zone macrophages (MZMs) and marginal zone metallophilic macrophages (MMMs), are highly heterogeneous as a consequence of adaptation to tissue-specific environments. Each macrophage sub-population in the spleen is usually identified based on the localization, morphology and membrane antigen expression by immunohistochemistry. However, their phenotypical and functional characteristics remain incompletely understood due to the difficulty of identification and isolation by flow cytometry.

Immunoreceptor CD300a on mast cells and dendritic cells regulates neutrophil recruitment in a murine model of sepsis.

Sepsis is a life-threatening syndrome caused by abnormal host immune responses against bacterial infection. Although innate immune cells are known to be important in the pathogenesis of sepsis, how their activation is regulated during sepsis remains incompletely understood. Here, we examined the role of the inhibitory immunoreceptor CD300a, which is expressed on various types of myeloid cells, in the pathogenesis of sepsis induced by cecal ligation and puncture (CLP).

Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling.

Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS).

Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces.

Epithelial tissues continually undergo apoptosis. Commensal organisms that inhabit the epithelium influence tissue homeostasis, in which regulatory T cells (Treg cells) have a central role. However, the physiological importance of epithelial cell apoptosis and how the number of Treg cells is regulated are both incompletely understood.

Involvement of CD300a Phosphatidylserine Immunoreceptor in Aluminum Salt Adjuvant-Induced Th2 Responses.

Aluminum salt (alum) has been widely used for vaccinations as an adjuvant. Alum not only enhances immunogenicity but also induces Th2 cell immune responses. However, the mechanisms of how alum enhances Th2 cell immune responses have been controversial.

Apoptotic cells suppress mast cell inflammatory responses via the CD300a immunoreceptor.

When a cell undergoes apoptosis, phosphatidylserine (PS) is exposed on the outer leaflet of the plasma membrane. PS acts as an "eat-me" signal to direct phagocytes expressing PS receptors to engulf the apoptotic cell. We recently reported that the immunoreceptor CD300a, which is expressed on myeloid cells, is a PS receptor.

Isolation and characterization of naïve follicular dendritic cells.

Follicular dendritic cells (FDC) are specialized antigen-presenting cells to cognate B cells in the follicle of the lymphoid tissues. FDC also support survival and proliferation of the B cells, leading to the germinal center formation. FDC therefore play a central role in humoral immune responses.

Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor.

CD300a is a member of CD300 family molecules consisting of seven genes on human chromosome 17 and nine genes in mouse chromosome 11. CD300a has a long cytoplasmic region containing the consensus immunoreceptor tyrosine-based inhibitory motif (ITIM) sequence. Upon crosslinking with antibodies against CD300a, CD300a mediates an inhibitory signal in myeloid cells.

The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses.

DAP12, an immunoreceptor tyrosine-based activation motif-bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B cells and B cells from a patient with Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12, showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated immune receptor.

Regulation of Immune Responses by the Activating and Inhibitory Myeloid-Associate Immunoglobuline-Like Receptors (MAIR) (CD300).

Activating and inhibitory cell surface receptors play important roles in regulation of immune responses. Recent progress has demonstrated that many inhibitory receptors pair with activating, as well as inhibitory, isoforms, both of whose genes are located in small clusters on a chromosome. We and others identified paired activating and inhibitory immunoglobulin-like receptors, designated myeloid-associated immunoglobulin-like receptors (MAIR) (CD300).

Caspase-independent cell death by CD300LF (MAIR-V), an inhibitory immunoglobulin-like receptor on myeloid cells.

The myeloid-associated Ig-like receptor family (CD300) consists of nine activating or inhibitory cell surface receptors preferentially expressed on myeloid cells and are encoded by the genes in a small cluster on mouse chromosome 11. One of the receptors, CD300LF (MAIR-V), has a long cytoplasmic tail containing two consensus ITIMs and an immunoreceptor tyrosine-based switching motif, suggesting that CD300LF regulates the activation of myeloid cells. However, the functional characteristics of this receptor are still incompletely understood.