Selective Function of PKC-θ in T cells

T cell activation is a critical process in initiating adaptive immune response since only through this process the naive antigen specific T cells differentiate into armed effector T cells that mediate the actual immune response. During T cell activation, naive T cells undergo clonal expansion and acquire the capability to kill target cells infected with pathogens or produce cytokines essential for regulating immune response. Inappropriate activation or inactivation of T cells leads to autoimmunity or severe immunodeficiencies. PKC-θ is selectively expressed in T cells and required for mediating T cell activation process. Mice deficient in PKC-θ exhibit defects in T cell activation, survival and activation-induced cell death. PKC-θ selectively translocates to immunological synapse and mediates the signals required for activation of NF-κB, AP1 and NFAT that are essential for T cell activation. Furthermore, PKC-θ^-│- mice displayed multiple defects in the development of T cell-mediated immune responses in vivo. PKC-θ is thus a critical molecule that regulates T cell function at multiple stages in T cell-mediated immune responses in vivo.     

Influence of a mutation in IFN-γ receptor 2 (IFNGR2) in human cells on the generation of Th17 cells in memory T cells

The T cell subsets involved in inflammatory reactions are mainly the IFN-γ secreting Th1 cells and IL17-producing Th17 cells. Although Th17 cells are primed in the thymus, there is evidence that Th17 cells can be generated from effector memory CD4⁺ T cells. Cytokines as IL-6, TGF-β, IL-21 and IL-23 involved in development of Th17 cells are well described. Here we analyzed the impact of a mutation in the IFN-γ receptor 2 (IFN-γR2) on the induction of Th17 cells. By isolation of T cells and monocytes of a patient with this mutation we could demonstrate an inhibitory role of IFN-γ signaling as IFN-γR2-deficient monocytes induce a higher percentage of IL-17⁺ cells from both healthy and IFN-γR2-deficient CD4⁺ T cells. This data confirm the interference of these two T helper subsets and points to a balance of Th1 and Th17 cells obtained by their own cytokine production and their interplay with APCs.     

Effect of classic convulsants on Cl<Superscript>−</Superscript> conductance of the GABA<Subscript>A</Subscript> receptor complex in membranes of cerebral cortex cells at the early stage of kindling

Muscimol-stimulated Cl- conductance of synaptoneurosomes from the cerebral cortex of Wistar rats increased during the early stage of pharmacological kindling not inducing the seizure response in animals. Picrotoxin, bicuculline, and pentylenetetrazole potentiated inhibition of muscimol-dependent 36Cl- entry into synaptoneurosomes, which attested to increased sensitivity of the GABA(A) receptor/Cl- ionophore complex to classic convulsants.     

The role of γδ T cells in the airways

Based on their T cell receptor expression two distinct T cell populations have been identified and designated as alphabeta and gammadelta T cells. While the specific role of alphabeta T cells is well understood, the specific function of gammabeta T cells remains elusive. Despite the limited knowledge on what gammadelta T cells exactly recognize as their antigen or antigens, several studies have clearly demonstrated that gammadelta T cells are important regulators of immune responses. Studies on gammadelta T cells in the lung have shown that gammadelta T cells influence B and T cell responses. For instance, gammadelta T cells modulate CD4+alphabeta T cells in tuberculosis, and in allergic inflammation they support IgE production. Furthermore, a recent study on their role as part of the innate immune response has demonstrated that gammadelta T cells regulate airway function independently of alphabeta T cells. This novel finding provides an opportunity to review previous studies on gammadelta T cells in the lung of mice and humans. The examination of these data demonstrates that understanding the role of the various subsets of gammadelta T cells will be critical in elucidating their function as "immunosurveillance cells" of the lung.     

Application of graphene-based nanomaterials in stem cells北大核心

BACKGROUND: As a kind of newly-developing nanomaterial, graphene has been used in many fields. Many recent studies have found that graphene-based nanomaterials can affect the biological behaviors of stem cells. OBJECTIVE: To review the application and progress of graphene-based nanomaterials in stem cells. METHODS: We searched the articles about the application of graphene-based nanomaterials in stem cells published in PubMed, Web of Science, and CNKI databases with the search terms “graphene, nanomaterials, stem cell” in English and Chinese. Finally, 57 articles met the criteria for review. RESULTS AND CONCLUSION: Graphene-based nanomaterials have good stability and corrosion resistance, high mechanical strength, good biocompatibility, which are accepted as one of the most promising nanomaterials in biomedicine. Stem cells are undifferentiated cells that can differentiate into various mature cells in human body, which have a broad application prospect in tissue engineering, regenerative medicine and other fields. Many recent studies have applied graphene-based nanomaterials to stem cell research and found that they can affect the growth, proliferation, adhesion and differentiation of stem cells, and these nanomaterials may affect the biological behavior of stem cells by regulating the expression of related genes and various signaling pathways. However, graphene-based nanomaterials have biological toxicity, which restrict their application in biological aspects. Moreover, most researches only involved cellular level, and it needs further animal studies and in vivo experimental researches. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Role of dendritic cells in Sjögren's syndrome

Sjögren's syndrome (SS) is a chronic inflammatory and lymphoproliferative autoimmune disease of unknown aetiology. It is characterised by progressive mononuclear cell infiltration of the salivary and lacrimal glands and a decreased glandular secretion, resulting in dryness of the mouth and eyes (xerostomia and keratoconjunctivitis sicca, respectively). Dendritic cells (DC) are considered to be the most potent antigen‐presenting cells. Because of their central role in initiating an immune response while maintaining tolerance, impaired function of these cells might lead to the break of peripheral tolerance and initiation of immune responses to self‐antigens. This review will focus on the possible role of DC in SS.     

Origin of bone-forming cells in human osteosarcomas transplanted into nude mice—which cells produce bone,human or mouse?

Osteosarcomas are malignant tumours producing osteoid and/or bone. It is difficult to distinguish tumour bone formation from reactive, based on their morphological features alone. The objective of this study was two-fold: to clarify the origins of bone-forming cells in human osteosarcoma transplanted into nude mice; and to examine the role of bone morphogenetic proteins (BMPs) in the tumour-induced osteogenesis. DNA in situ hybridization was carried out with digoxigenin (DIG) polymerase chain reaction (PCR) labelled DNA probes for human-specific ‘Alu’ and mouse-specific ‘mouse L1 (m-L1)’ genes. Human osteosarcoma cells, established cell lines of NOS-1, NOS-2, and HuO9, were transplanted separately into nude mice. Bone-forming cells of the bone in the NOS-1 or NOS-2 tumours were positive for Alu, while they were negative for m-L1. The cells lining the surface of trabeculae in the HuO9 tumour were positive for Alu, but a few of them were also positive for m-L1. The m-L1-positive cells expressed mouse osteocalcin and type I collagen mRNAs. These facts suggest that the mouse cells were involved in osteoid synthesis of the HuO9 tumour. The NOS-1 or NOS-2 tumours expressed human BMP 2–7 mRNAs, whereas the HuO9 tumour expressed human BMPs 2, 4, 5, and 7. The osteogenetic potential of the tumours may depend on the expression patterns of BMPs. These results demonstrate two distinct types of bone formation, by tumour cells and by an admixture of tumour and non-tumour cells. The present study showed that the HuO9 tumour produces chimeric bone formation. This is the first report to demonstrate the relationships between tumour cells and non-tumour cells in bone formation, using genetic markers. © 1998 John Wiley & Sons, Ltd.     

Essential roles of SIRPα in homeostatic regulation of skin dendritic cells

Signal regulatory protein α (SIRPα) is an immunoglobulin superfamily protein that is predominantly expressed in dendritic cells (DCs). Its cytoplasmic region binds SHP-1 or SHP-2 protein tyrosine phosphatases, while its extracellular region interacts with CD47, another immunoglobulin superfamily protein, constituting cell-cell signaling. SIRPα was previously shown to be important for development of contact hypersensitivity, likely as a result of its positive regulation of the priming by DCs of CD4(+) T cells. However, the mechanism by which SIRPα regulates DC functions remains unknown. Here we found that the number of I-A(+) cells, which represent migratory DCs such as Langerhans cells (LCs) or dermal DCs from the skin, in the peripheral lymph nodes (LNs) was markedly decreased in mice expressing a mutant form of SIRPα that lacks the cytoplasmic region compared with that of wild-type (WT) mice. In addition, an increase of fluorescein isothiocyanate (FITC)-bearing I-A(+) cells in the draining lymph nodes (LNs) after skin-painting with FITC was markedly blunted in SIRPα mutant mice. However, migratory ability, as well as expression of CCR7, of bone marrow-derived DCs prepared from SIRPα mutant mice were not impaired. By contrast, the number of I-A(+) LCs in the epidermis of SIRPα mutant mice was markedly decreased compared with that of WT mice. In addition, the mRNA expression of transforming growth factor-β receptor II in LCs of SIRPα mutant mice was markedly decreased compared with that of WT mice. These results suggest that SIRPα is important for homeostasis of LCs in the skin, as well as of migratory DCs in the LNs, but unlikely for migration of these cells from the skin to draining LNs.     

Role of the β<Subscript>1</Subscript>-integrin subunit in the adhesion,extravasation and migration of T24 human bladder carcinoma cells

The abilities of tumor cells to extravasate from the blood vessel system and to migrate through the connective tissue are prerequisites in metastasis formation. Both processes are chiefly mediated by integrins, which mediate both cell–cell and cell–matrix interactions. We investigated the role of integrin subunits in the adhesion, extravasation and migration of the highly invasive human bladder carcinoma cell line T24. Here we show that inhibition of the β₁-integrin subunit using the specific β₁-integrin blocking antibody 4B4 significantly reduces the adhesion to HUVEC and transmigratory activity of T24 cells. The blockade of the β₁-integrin subunit also resulted in a significantly reduced locomotory activity of T24 cells. A detailed cell migration analysis on a single cell level revealed that blockade of the β₁-integrin subunit leads to an altered migration pattern of single cells but does not influence migration per se. Migration parameters such as time active, velocity and distance migrated were significantly reduced as compared to untreated control cells. Our observations strongly suggest a central role for the β₁-integrin subunit in forming the cell–cell and cell–matrix bonds necessary for adhesion, extravasation and migration.     

Episomal replication timing of γ-herpesviruses in latently infected cells

This study addresses the timing of gammaherpesviral episomal DNA replication with respect to the cell cycle. For the first time we analyzed a rhadinovirus, the prototype Herpesvirus saimiri (HVS), and compared it to the lymphocryptovirus Epstein-Barr virus (EBV). Newly synthesized DNA of latently infected B- or T-cells was first BrdU-labeled; then we sorted the cells corresponding to cell cycle phases G_0/1, G_2/M, and S (4 fractions S₁-S₄) and performed anti-BrdU chromatin immunoprecipitation. Next, DNA of different viral gene loci was quantitatively detected together with cellular control genes of known replication time. The sensitive technique is further enhanced by an internal coprecipitation standard for increased precision. Both gammaherpesviruses replicated very early in S-phase, together with cellular euchromatin. Our work suggests that early S-phase DNA replication is a general characteristic of episomal herpesviral genomes.     

Expression of natriuretic peptides in rat Müller cells

Natriuretic peptides (NPs) have been shown to modulate neuronal activities. By immunohistochemistry and confocal microscopy, we examined expression of atrial NP (ANP), brain NP (BNP) and C-type NP (CNP) in rat retina. Our results showed that these peptides were differentially expressed in the neural retina. While strong ANP-, BNP- and CNP-immunoreactivity (IR) was clearly seen in the outer and inner plexiform layers and on numerous neurons in the inner nuclear layer, BNP- and CNP-, but not ANP-IR, was present in some ganglion cells. Furthermore, ANP, BNP and CNP were expressed in Müller cells with distinct profiles, as shown by double labeling of NPs and vimentin. Labeling for BNP was rather strong in the main trunks, major processes, but hardly detectable in the endfeet. The expression profile for ANP was similar, but with a much lower level. On the contrary, the endfeet and major processes in the inner retina were strongly CNP-positive, with the main trunks and other major processes in the outer retina much less labeled. These results raise a possibility that NPs, when released from Müller cells, may perform layer dependent functions.     

Polarization of B effector cells in Sjögren's syndrome

Analysis of salivary glands of patients with primary Sj?gren's syndrome has yielded conflicting results with respect to T helper (Th)1/Th2 polarization. This balance might parallel the progress of the local lesions. B-cells are now taking center stage in this disease. They can also be primed to differentiate into two cytokine-production pathways, dubbed B effector (Be) 1 and Be2 cells. This is discussed in the light of our recent finding that Be1 accompany Th1, while Be2 accompany in the tissue lesions.     

Alterations in T cells of cancer-bearers: whence specificity?

T cells of tumor-bearing mice and cancer patients have been reported to have altered signal-transduction machinery. These alterations have been implicated in immunological suppression. Here, Daniel Levey and Pramod Srivastava critically examine the evidence for these alterations in the context of the tumor specificity of immunological unresponsiveness in tumor-bearing hosts.     

Important role of glutathione in stemness and regulation of stem cells北大核心

BACKGROUND: Stem cells possess the capacities of self-renewal and multiple differentiation. Glutathione, an important sulfhydryl compounds, not only participates in the active oxygen metabolism of stem cells, but also plays an important role in self-renewal, proliferation, aging, stemness maintenance and differentiation regulation of stem cells. OBJECTIVE: To explore the important role of glutathione in stem cells. METHODS: In April 2020, the first author searched the title/abstract with the English keywords of “glutathione or GSH, stem cell”, and searched any field with the Chinese keywords of “glutathione, stem cell”, and searched the related articles included in CNKI, VIP, Wanfang and PubMed databases from 2000 to 2020. A total of 358 Chinese articles and 405 English articles were retrieved. Finally, 86 eligible articles were enrolled for the analysis after deleting the repetitive and non-conforming articles. RESULTS AND CONCLUSION: By reviewing the recent studies on glutathione and stem cells, we found that glutathione played an important role in maintaining stemness, regulating the differentiation of stem cells. In addition, effects of glutathione on cancer stem cells have been verified, which provides more evidence for the future treatment of cancer with reduced glutathione. Key words:. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Insulin-like growth factors 1 and 2 regulate expression of β-casein <Emphasis Type="Italic">in vitro</Emphasis> in mouse mammary epithelial cells

We studied the role of insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) in functional differentiation of HC11 mouse mammary gland cells. It was found that both IGF-1 and IGF-2 activate the expression of milk protein β-casein in the presence of prolactin and hydrocortisone. It was found that β-casein expression is accompanied by cyclin D1 coexpression.     

In vitro immunostimulatory potential of fungal β-glucans in pacific red snapper (Lutjanus peru) cells

This study attempts to describe the immunostimulatory effects of three fungal glucans on innate immunity responses in an in vitro assays using Pacific red snapper leukocytes. First, the yield glucans obtained was higher in Aspergillus niger, follow by Aspergillus ochraceus and Alternaria botrytis (40, 20 and 10%, respectively). Structural characterization of these fungal glucans by proton nuclear magnetic resonance (NMR) indicated structures containing (1–6)-branched (1–3)-β-D-glucan. The immunostimulatory activity of fungal glucans were assessed in head-kidney leukocytes at 24 h using colorimetric assays and molecular gene expression. In addition, the response against bacterial infection using Aeromonas hydrophila was evaluated by flow cytometry with annexin V/propidium iodide. Leukocytes responded positively to fungal glucans where the viability was higher than 80%. Interestingly, A. niger β-glucans enhanced the phagocytic ability and capacity in head-kidney leukocytes. Immunological assays reveled an increased in nitric oxide production, myeloperoxidase, superoxide dismutase and catalase activities, in fish stimulated with A. niger β-glucans. Induction of cytokines (IL-1β, TNF-α, IL-6, IL-8 and IL-12) were more pronounced in A. niger β-glucans leukocytes stimulated compared to other group. Finally, flow cytometry assay showed that A. botrytis and A. niger β-glucans were able to inhibit apoptosis caused by Aeromonas hydrophila in the Pacific red snapper leukocytes indicating an immunostimulant potent response by fungi derived-glucans. These results strongly support the idea that fungal β-glucans can stimulate the immune mechanism in head-kidney leukocytes and that Aspergillus niger β-glucan possess immunostimulatory properties cell increasing viability, and reducing necrotic cell death caused by Aeromonas hydrophila.