Therapeutic Effect of IL1β Priming Tonsil Derived-Mesenchymal Stem Cells in Osteoporosis.

Background: Stem cell therapies can be a new therapeutic strategy that may rebalance anabolic and anti-resorptive effects in osteoporosis patients. Tonsil-derived mesenchymal stem cells (TMSCs) can be an alternative therapeutic source for chronic degenerative diseases including osteoporosis. MSCs acquire immune regulatory function under the inflammatory cytokines.

Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells.

Lysine acetylation regulates transcription by targeting histones and nonhistone proteins. Here we report that the central regulator of transcription, RNA polymerase II, is subject to acetylation in mammalian cells. Acetylation occurs at eight lysines within the C-terminal domain (CTD) of the largest polymerase subunit and is mediated by p300/KAT3B.

Two-pronged binding with bromodomain-containing protein 4 liberates positive transcription elongation factor b from inactive ribonucleoprotein complexes.

The positive transcription elongation factor b (P-TEFb) exists in two forms in cells as follows: an inactive form where the core components cyclin T1 and CDK9 are incorporated in the 7SK small nuclear ribonucleoprotein complex containing the inhibitory molecule HEXIM1, and an active form, part of which associates with the bromodomain-containing protein BRD4. Here, we define a novel interaction between P-TEFb and BRD4 involving tri-acetylated cyclin T1 (acK380, acK386, and acK309) and the second bromodomain in BRD4. This interaction is observed with the short splice variant of BRD4 (amino acids 1-722) lacking a previously defined C-terminal P-TEFb-interacting domain (PID).

CYCLINg through transcription: posttranslational modifications of P-TEFb regulate transcription elongation.

The cyclin T/CDK9 complex, also called positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of the large fragment of the RNA polymerase II. This action is a hallmark of the transition from transcription initiation to elongation. P-TEFb is itself modified by phosphorylation and ubiquitination.

A threonine-based targeting signal in the human CD1d cytoplasmic tail controls its functional expression.

CD1d molecules are MHC class I-like molecules that present lipids to a unique subpopulation of T cells called NKT cells. The cytoplasmic tail of human CD1d possesses a tyrosine-based endosomal targeting motif (YXXZ). As such, these molecules traffic through the endocytic pathway, where it is believed that they are loaded with the antigenic lipid that stimulates NKT cells.

Acetylation of cyclin T1 regulates the equilibrium between active and inactive P-TEFb in cells.

The elongation competence of the RNA polymerase II complex is critically dependent on the positive transcription elongation factor b (P-TEFb). P-TEFb exists in two forms in cells, an active form composed of cyclin T1 and CDK9 and an inactive form, in which cyclin T1/CDK9 is sequestered by Hexim1 and 7SK snRNA. Here, we report that partitioning of active and inactive P-TEFb is regulated by acetylation of cyclin T1.

Impaired cell surface expression of human CD1d by the formation of an HIV-1 Nef/CD1d complex.

The HIV-1 Nef protein causes a decrease in major histocompatibility complex (MHC) class I and CD4 molecule expression on the cell surface. To determine if Nef can affect components of the innate immune response, we assessed the ability of Nef to alter the cell surface expression of human CD1d. In cells co-expressing CD1d and Nef, a substantial reduction in the cell surface level of CD1d was observed, with a concomitant reduction in the activation of CD1d-restricted NKT cells.

Human immunodeficiency virus gp120 downregulates CD1d cell surface expression.

CD1d is an MHC class I-like surface molecule that presents endogenous glycoplipid antigens. The effect of HIV infection on CD1d surface expression has not yet been reported. FACS analysis revealed significantly lower levels of CD1d on CD14(+) monocytes from HIV-infected subjects compared to HIV-infected subjects on HAART and healthy controls.

Long-term loss of canonical NKT cells following an acute virus infection.

NKT cell activation plays an important role in regulating innate and adaptive immunity during infection. We have previously found that there is a dramatic reduction in the NKT cell population on day 3 after an acute lymphocytic choriomeningitis virus (LCMV) infection. In this study, we report that this loss continued for at least 3 months and was not simply due to internalization of the TCR.

CD1d-mediated antigen presentation to natural killer T (NKT) cells.

CD1d molecules are lipid antigen-presenting molecules. They are involved in presenting these antigens to a unique subpopulation of T cells called natural killer T (NKT) cells, which have the capacity to produce both T helper (Th) 1 and Th2 cytokines. Thus, it is possible that the antigens presented by CD1d and/or the level at which they are presented could have profound effects on the immunoregulation of autoimmune and infectious diseases, as well as cancer.

Myeloid marker expression on antiviral CD8+ T cells following an acute virus infection.

CD11b, CD11c, and F4/80 are normally used to define dendritic cell and/or macrophage populations. In this study, the expression of all three markers was observed on CD8(+) T cells following infection of mice with several distinct viruses. Using lymphocytic choriomeningitis virus as a model virus, it was found that relatively more CD11b(+)CD8(+) and CD11c(+)CD8(+) T cells were present in the periphery than in primary lymphoid organs; in contrast, the F4/80(+)CD8(+) T cell population was more prevalent in the spleen.

Inhibition of glycolipid shedding rescues recognition of a CD1+ T cell lymphoma by natural killer T (NKT) cells.

Neoplastic transformation of cells is accompanied by an aberration of cell surface glycolipid composition. These tumor-associated, altered glycosphingolipids are often shed into the tumor cell microenvironment and mediate immunosuppressive activity. The nature and form of glycolipids shed by a variety of tumor cell lines and the mechanism(s) of shedding have been well characterized.