Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.

Background: The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors.

Polymorphic Sirpa is the genetic determinant for NOD-based mouse lines to achieve efficient human cell engraftment.

Current mouse lines efficient for human cell xenotransplantation are backcrossed into NOD mice to introduce its multiple immunodeficient phenotypes. Our positional genetic study has located the NOD-specific polymorphic Sirpa as a molecule responsible for its high xenograft efficiency: it recognizes human CD47 and the resultant signaling may cause NOD macrophages not to engulf human grafts. In the present study, we established C57BL/6.

Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers.

Tumor development is a complex and dynamic process that involves malignant, vascular, and stromal cells. Endosialin is a tumor endothelial marker (TEM) present in the microvasculature and stroma of human tumors. Cancer-associated fibroblasts (CAF) have been implicated in promoting tumor development and have been associated with mesenchymal stem cells (MSC).

Endosialin protein expression and therapeutic target potential in human solid tumors: sarcoma versus carcinoma.

Purpose: Endosialin/CD248/tumor endothelial marker 1 is expressed in stromal cells, endothelial cells, and pericytes in various tumors; however, few studies have focused on expression in malignant cells.

Experimental Design: We studied expression of endosialin in clinical specimens, cell culture, and animal models and designed an anti-endosialin therapeutic prototype.

Results: Fifty human tumor cell lines and 6 normal cell types in culture were assayed by reverse transcription-PCR and/or flow cytometry for endosialin.

Endosialin/TEM 1/CD248 is a pericyte marker of embryonic and tumor neovascularization.

The formation of functional, mature blood vessels depends on the interaction between endothelial cells and pericytes. Commonality exists in the processes involved in vasculature development between tissues whether healthy or diseased. Endosialin/TEM 1 is a cell membrane protein that is expressed in blood vessels during embryogenesis and tumorigenesis but not in normal mature vessels.

Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC.

Structural insight into the specific interaction between murine SHPS-1/SIRP alpha and its ligand CD47.

SRC homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1 or SIRP alpha/BIT) is an immunoglobulin (Ig) superfamily transmembrane receptor and a member of the signal regulatory protein (SIRP) family involved in cell-cell interaction. SHPS-1 binds to its ligand CD47 to relay an inhibitory signal for cellular responses, whereas SIRPbeta, an activating member of the same family, does not bind to CD47 despite sharing a highly homologous ligand-binding domain with SHPS-1. To address the molecular basis for specific CD47 recognition by SHPS-1, we present the crystal structure of the ligand-binding domain of murine SHPS-1 (mSHPS-1).

Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation.

Recently, we reported that Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) plays an important role in the migration of Langerhans cells (LC). Here, we show that SHPS-1 is involved in the maturation of LC. Immunofluorescence analysis on epidermal sheets for I-A or CD86 revealed that LC maturation induced by 2,4-dinitro-1-fluorobenzene (DNFB) or by TNF-alpha was inhibited by pretreatment with an anti-SHPS-1 monoclonal antibody (mAb) or with CD47-Fc fusion protein, a ligand for SHPS-1.

Engagement of CD47 inhibits the contact hypersensitivity response via the suppression of motility and B7 expression by Langerhans cells.

CD47 is a membrane-associated glycoprotein that suppresses the function of immune cells. We previously reported that Langerhans cells (LCs) express Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1), a ligand for CD47, which plays an important role in the regulation of their motility. In this study, we show that LCs also express CD47, and that ligation of CD47 with SHPS-1-Fc fusion protein in vivo diminishes the development of the contact hypersensitivity response.

SHPS-1 negatively regulates integrin alphaIIbbeta3 function through CD47 without disturbing FAK phosphorylation.

CD47 (integrin-associated protein) serves as a receptor for thrombospondin-1 (TSP-1) and Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1), and the TSP-1/CD47 interaction has been believed to augment integrin-mediated platelet function. Here, employing SHPS-1-immunoglobulin (Ig) as a ligand, we have newly demonstrated that CD47 acts as an inhibitory receptor for platelet function. The binding of SHPS-1-Ig was solely mediated by CD47, because CD47-deficient platelets failed to bind murine SHPS-1-Ig.

Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the migration of Langerhans cells from the epidermis to draining lymph nodes.

Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) is a member of the signal regulatory protein family in which the extracellular region interacts with its ligand, CD47. Recent studies have demonstrated that SHPS-1 plays an important role in cell migration and cell adhesion. We demonstrate in this study, using immunohistochemical and flow cytometric analyses, that murine Langerhans cells (LCs) express SHPS-1.

Resistance of B16 melanoma cells to CD47-induced negative regulation of motility as a result of aberrant N-glycosylation of SHPS-1.

The adhesion receptor SHPS-1 activates the protein-tyrosine-phosphatase SHP-2 and thereby promotes integrin-mediated reorganization of the cytoskeleton. SHPS-1 also contributes to cell-cell communication through association with CD47. Although functional alteration of SHPS-1 is implicated in cellular transformation, the role of the CD47-SHPS-1 interaction in carcinogenesis has been unclear.

Regulation of multiple functions of SHPS-1, a transmembrane glycoprotein, by its cytoplasmic region.

SHPS-1 is a receptor-type transmembrane glycoprotein, which contains four tyrosine residues in its cytoplasmic region, and the phosphorylation of these tyrosine residues serves the binding sites for SHP-2 protein-tyrosine phosphatase. Its extracellular region interacts with another membrane protein, CD47, thereby constituting a cell-cell communication system. We analyzed this ligand-receptor interaction using Chinese hamster ovary (CHO) cells expressing wild-type (WT) or mutant SHPS-1.

Role of the CD47-SHPS-1 system in regulation of cell migration.

SHPS-1 is a transmembrane protein whose extracellular region interacts with CD47 and whose cytoplasmic region undergoes tyrosine phosphorylation and there by binds the protein tyrosine phosphatase SHP-2. Formation of this complex is implicated in regulation of cell migration by an unknown mechanism. A CD47-Fc fusion protein or antibodies to SHPS-1 inhibited migration of human melanoma cells or of CHO cells overexpressing SHPS-1.

Interaction between Src homology 2 domain bearing protein tyrosine phosphatase substrate-1 and CD47 mediates the adhesion of human B lymphocytes to nonactivated endothelial cells.

CD47 modulates a variety of cell functions such as adhesion, spreading, and migration. Using a fusion protein consisting of the extracellular region of Src homology 2 domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1) and the Fc portion of human Ig (SHPS-1-Ig) we investigated the effects of SHPS-1 as a ligand for CD47 on B lymphocytes. Although SHPS-1-Ig binding to human B cell lines was solely mediated via CD47, their binding capacity for soluble and immobilized SHPS-1-Ig varied among cell lines irrespective of the similar expression levels of CD47, suggesting that distinctive affinity/avidity states exist during B cell maturation.