-
Biochemical and Biophysical Research... May 2022CD99 is a glycoprotein primarily expressed in immune cells. Physiologically, it is involved in the adhesion, migration, and development of immune cells. The presence of...
CD99 is a glycoprotein primarily expressed in immune cells. Physiologically, it is involved in the adhesion, migration, and development of immune cells. The presence of CD99 in the skin was first reported in 2016 and its function is yet to be determined. In this study, we aimed to understand the role of CD99 in the skin using normal human epidermal keratinocytes (NHEK). CD99 expression increased with the confluency of NHEK, while the CD99-high expressing NHEK lost their stem cell properties and played a role in barrier function. We characterized CD99-expressing NHEK as cells committed to early differentiation because they expressed early differentiation markers. However, the deficiency of CD99 in NHEK disrupted homeostasis and caused aberrant differentiation, as evidenced by larger cells with lesser Ki67 staining and higher expression of terminal differentiation markers. Hence, we propose that CD99 is involved in maintaining homeostasis and initiating early differentiation in the skin.
Topics: 12E7 Antigen; Antigens, Differentiation; Cell Differentiation; Cells, Cultured; Epidermis; Homeostasis; Humans; Keratinocytes
PubMed: 35339749
DOI: 10.1016/j.bbrc.2022.03.087 -
Biochimica Et Biophysica Acta Jun 2016The invariant chain (CD74) is well known for its essential role in antigen presentation by mediating assembly and subcellular trafficking of the MHCII complex. Beyond... (Review)
Review
The invariant chain (CD74) is well known for its essential role in antigen presentation by mediating assembly and subcellular trafficking of the MHCII complex. Beyond this, CD74 has also been implicated in a number of processes independent of MHCII. These include the regulation of endosomal trafficking, cell migration and cellular signalling as surface receptor of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF). In several forms of cancer, CD74 is up-regulated and associated with enhanced proliferation and metastatic potential. In this review, an overview of the diverse biological functions of the CD74 protein is provided with a particular focus on how these may be regulated. In particular, proteolysis of CD74 will be discussed as a central mechanism to control the actions of this important protein at different levels.
Topics: Animals; Antigen Presentation; Antigens, Differentiation, B-Lymphocyte; Histocompatibility Antigens Class II; Humans; Models, Immunological; Molecular Chaperones; Neoplasm Metastasis; Neoplasms; Receptors, Immunologic; Up-Regulation
PubMed: 27033518
DOI: 10.1016/j.bbamcr.2016.03.026 -
Scientific Reports Jun 2024The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis...
The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis that serve as biological and structural scaffolds for the development of the dermal tissue. To investigate the dermal structure, the current study used morphological and immunological techniques. TCs identified by TEM. They had a cell body and unique podomeres and podoms. They formed a 3D network spread throughout the dermis. Homocellular contact established between them, as well as heterocellular contacts with other cells. Immunohistochemical techniques using specific markers for TCss CD34, CD117, and VEGF confirmed TC identification. TCs represent the major interstitial component in the dermal tissue. They established a 3D network, enclosing other cells and structures. Expression of VEGF by TC promotes angiogenesis. TCs establish cellular contact with sprouting endothelial cells. At the site of cell junction with TCs, cytoskeletal filaments identified and observed to form the pseudopodium core that projects from endothelial cells. TCs had proteolytic properties that expressed MMP-9, CD68, and CD21. Proteolytic activity aids in the removal of components of the extracellular matrix and the phagocytosis of degraded remnants to create spaces to facilitate the development of new dermal structures. In conclusion, TCs organized the scaffold for the development of future dermal structures, including fibrous components and skin appendages. Studying dermal TCs would be interested in the possibility of developing therapeutic strategies for treating different skin disorders and diseases.
Topics: Telocytes; Immunohistochemistry; Dermis; Humans; Antigens, CD34; Animals; Vascular Endothelial Growth Factor A; Antigens, CD; Matrix Metalloproteinase 9; Endothelial Cells; Antigens, Differentiation, Myelomonocytic; CD68 Molecule
PubMed: 38886354
DOI: 10.1038/s41598-024-63802-5 -
Blood Advances Sep 2023The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed toward the tumor immune microenvironment, where...
The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed toward the tumor immune microenvironment, where macrophages play an important role. In MCL, the presence of M2 macrophages defined by CD163 expression in diagnostic biopsies has been associated with a worse prognosis. An alternative way to assess the abundance of M2 macrophages is by measuring the level of soluble CD163 in serum (sCD163). We aimed to investigate the prognostic value of sCD163 in 131 patients with MCL. We found that high sCD163 at diagnosis was associated with shorter progression-free survival (PFS) and shorter overall survival (OS) in 81 patients who were newly diagnosed and subsequently treated with chemoimmunotherapy. The same was seen in a cohort of 50 patients with relapsed MCL that were mainly treated within the phase 2 Philemon-trial with rituximab, ibrutinib, and lenalidomide. In patients who were newly diagnosed and had low levels of sCD163, 5-year survival was 97%. There was a moderate correlation between sCD163 and tissue CD163. The association with a poor prognosis was independent of MCL international prognostic index, Ki67, p53 status, and blastoid morphology, as assessed in a multivariable Cox proportional hazards model. In this study, high sCD163 was associated with both shorter PFS and shorter OS, showing that high levels of the M2 macrophage marker sCD163 is an independent negative prognostic factor in MCL, both in the chemoimmunotherapy and ibrutinib/lenalidomide era. In addition, low sCD163 levels identify patients with MCL with a very good prognosis.
Topics: Adult; Humans; Lymphoma, Mantle-Cell; Lenalidomide; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Tumor Microenvironment
PubMed: 37389827
DOI: 10.1182/bloodadvances.2023010052 -
Stem Cell Research Dec 2019Human teratoma is a germ cell tumor that contains normal tissues (e.g., hair, skin or cartilage) differentiated from embryonal germ layers. Because of the feature of...
Human teratoma is a germ cell tumor that contains normal tissues (e.g., hair, skin or cartilage) differentiated from embryonal germ layers. Because of the feature of this tumor, we hypothesized that human teratomas contain multipotent stem cells that can develop into various non-cancerous normal tissues. In this study, we cultured neurospheres originally derived from a human infantile teratoma tissue, and the sphere cells were found to possess the characteristics of neural stem cells. Tumor tissues were obtained from an infantile immature teratoma at the time of surgical resection. In the primary cell culture, colonies were formed in two weeks and were individually cultured in serum-free conditioned neural stem cell medium (NSC medium). Colonies changed into spheres and grew in smooth round forms, or attached to the bottom of the dishes and extended processes and filaments around. Sphere cells were dissociated into single cells, and new spheres (secondary spheres) were formed in NSC medium. Cell differentiation was induced by culturing cells in serum-containing medium (differentiation medium), as cells spread and attached to the bottom of dishes and changed form. The expression of Nestin, Sox2, CXCR4, and (stem cell markers), β3-tubulin (a neural marker) GFAP (a glial marker) CNPase, SOX10 (oligodendrocyte markers) and NF-L in cells was analyzed by immunofluorescence and a Q-PCR. Nestin, SOX2, CXCR4 were abundant in both primary and secondary spheres. Neural and glial markers (β3-tubulin and GFAP, respectively) were increased in cells cultured in differentiation medium while stem cell markers were diminished. The oligodendrocyte markers SOX10 and CNPase were also found in both spheres and differentiated cells. In conclusion, spheres with the characteristics of neural stem cells were obtained from the primary culture of a human infantile teratoma. These spheres are considered to have the potential to undergo a natural course of neural development in humans.
Topics: Antigens, Differentiation; Humans; Multipotent Stem Cells; Neural Stem Cells; Teratoma
PubMed: 31733440
DOI: 10.1016/j.scr.2019.101633 -
Immunology Aug 2019The study of cellular and molecular immunology is almost completely dependent on monoclonal antibody technology. Despite the relatively long history of monoclonal...
The study of cellular and molecular immunology is almost completely dependent on monoclonal antibody technology. Despite the relatively long history of monoclonal antibodies, there is still huge potential for developing novel and transformative uses for this technology. In this issue of Immunology, we present two such papers, one focussing on anti-complement (C5) antibodies, the other on anti-CD6-specific antibodies. Both manuscripts describe novel ways that monoclonal antibodies may be used for scientific and potentially for therapeutic benefit.
Topics: Animals; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Complement C5; Humans
PubMed: 31291693
DOI: 10.1111/imm.13092 -
Journal of Innate Immunity 2019Early exposure to inflammatory signals may have a lasting impact on immune function. Present throughout embryogenesis, macrophages are key cells providing innate immune...
Early exposure to inflammatory signals may have a lasting impact on immune function. Present throughout embryogenesis, macrophages are key cells providing innate immune protection to the developing fetus and newborn. Here, we have used an established model of macrophage development to test how early inflammatory signals can impact cellular differentiation and function. Bone marrow-derived macrophages were treated with Escherichia coli lipopolysaccharide (LPS) 2 days after initial isolation and culture. LPS treatment during this early stage of differentiation decreased the expression of CSF1R and increased that of the mature macrophage marker F4/80. These early changes in macrophage differentiation were also measured in cells from mice lacking IKKβ, but the change in CSF1R expression after LPS treatment was blocked with MAPK inhibition. LPS-induced changes in macrophage marker expression persisted following LPS removal, suggesting that early inflammatory activation could induce a lasting developmental impact. Early LPS exposure inhibited macrophage phagocytosis of labeled E. coli while LPS had no effect on fully differentiated macrophages. Our data demonstrate that early inflammatory exposure to a microbial stimulus induce lasting phenotypic changes in macrophages.
Topics: Animals; Antigens, Differentiation; Calcium-Binding Proteins; Cell Differentiation; Escherichia coli; I-kappa B Kinase; Immunity, Innate; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Mitogen-Activated Protein Kinases; Phagocytosis; Receptors, G-Protein-Coupled; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Signal Transduction; Toll-Like Receptors
PubMed: 30408777
DOI: 10.1159/000494070 -
Biomaterials Science Jan 2016Chemotherapy has been adopted for cancer treatment for decades. However, its efficacy and safety are frequently compromised by the multidrug-resistance of cancer cells...
Chemotherapy has been adopted for cancer treatment for decades. However, its efficacy and safety are frequently compromised by the multidrug-resistance of cancer cells and the poor cancer cell selectivity of anticancer drugs. Hereby, we report a combination of a pyridine-2-thiol containing polymer and copper which can effectively kill a wide spectrum of cancer cells, including drug resistant cancer cells, while sparing normal cells. The polymer nanoparticle enters cells via an exofacial thiol facilitated route, and releases active pyridine-2-thiol with the help of intracellularly elevated glutathione (GSH). Due to their high GSH level, cancer cells are more vulnerable to the polymer/copper combination. In addition, RNA microarray analysis revealed that the treatment can reverse cancer cells' upregulated oncogenes (CIRBP and STMN1) and downregulated tumor suppressor genes (CDKN1C and GADD45B) to further enhance the selectivity for cancer cells.
Topics: Antigens, Differentiation; Antineoplastic Agents; Cell Line, Tumor; Copper; Down-Regulation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Glutathione; Humans; Nanoparticles; Organometallic Compounds; Polymers; Pyridines; RNA-Binding Proteins; Sulfhydryl Compounds; Up-Regulation
PubMed: 26568413
DOI: 10.1039/c5bm00325c -
Proceedings of the Japan Academy.... 2018The antibody response to RNA-related antigens such as Sm/RNP requires the endosomal RNA sensor TLR7, and this process is crucial in the development of systemic lupus... (Review)
Review
The antibody response to RNA-related antigens such as Sm/RNP requires the endosomal RNA sensor TLR7, and this process is crucial in the development of systemic lupus erythematosus at least in animal models. The inhibitory B cell receptor CD72 is unique because it recognizes Sm/RNP and specifically inhibits the activation of Sm/RNP-reactive B cells by activating SH2-containing protein tyrosine phosphatase 1 (SHP-1). In the normal immune system, Sm/RNP-reactive B cells are tolerized by a unique mechanism that probably involves SHP-1. These self-reactive B cells appear in the peripheral lymphoid organs, differentiate into marginal zone B cells, and then undergo apoptosis without further maturation into plasma cells. Thus, CD72 is involved in the suppression of TLR7-mediated response to RNA in complexes with nuclear proteins that are resistant to nucleases, whereas free RNAs are degraded by nucleases before they encounter the endosomal RNA sensor.
Topics: Animals; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Autoantigens; B-Lymphocytes; Down-Regulation; Humans; Immune Tolerance; Lupus Erythematosus, Systemic; Protein Tyrosine Phosphatase, Non-Receptor Type 6; RNA; Ribonucleoproteins, Small Nuclear; Signal Transduction; Toll-Like Receptor 7
PubMed: 29321445
DOI: 10.2183/pjab.94.003 -
Scientific Reports Jul 2021The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA...
The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.
Topics: Adult; Aged; Aged, 80 and over; Antigens, Differentiation; Apoptosis; Cell Cycle Proteins; Dendritic Cells; Epigenesis, Genetic; Female; Humans; Inflammation; Keratinocytes; Male; Methylation; Middle Aged; Psoriasis; Skin; T-Lymphocytes; Ubiquitin Thiolesterase
PubMed: 34272424
DOI: 10.1038/s41598-021-93780-x