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Mesenchymal stem cells in health and disease
The targets and mechanisms of M SC-mediated immunomodulation and the possible translation of MSCs to new therapeutic approaches are discussed.
Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis.
The discovery of MHC-specific inhibitory receptors in mouse and in human clarified the molecular basis of this important NK cell function, and some of these receptors have now been identified in humans, thus shedding some light on the molecular mechanisms involved in NK cell activation during the process of natural cytotoxicity.
Identification and Molecular Characterization of Nkp30, a Novel Triggering Receptor Involved in Natural Cytotoxicity Mediated by Human Natural Killer Cells
NKp30 is identified, a novel 30-kD triggering receptor selectively expressed by all resting and activated human natural killer (NK) cells, and is associated with CD3ζ chains that become tyrosine phosphorylated upon sodium pervanadate treatment of NK cells.
Identification of PVR (CD155) and Nectin-2 (CD112) as Cell Surface Ligands for the Human DNAM-1 (CD226) Activating Molecule
- C. Bottino, R. Castriconi, A. Moretta
- Biology, ChemistryThe Journal of experimental medicine
- 18 August 2003
The surface expression of PVR or Nectin-2 in cell transfectants resulted in DNAM-1–dependent enhancement of NK-mediated lysis of these target cells, and this lysis was inhibited or even virtually abrogated upon mAb-mediated masking of DNam-1 (on NK cells) or PVR and NectIn-2 ligands (on celltransfectants).
NKp44, a Novel Triggering Surface Molecule Specifically Expressed by Activated Natural Killer Cells, Is Involved in Non–Major Histocompatibility Complex–restricted Tumor Cell Lysis
It is shown that p46 and NKp44 are coupled to the intracytoplasmic transduction machinery via the association with CD3ζ or KARAP/DAP12, respectively; these associated molecules are tyrosine phosphorylated upon NK cell stimulation.
Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation.
- G. Spaggiari, A. Capobianco, S. Becchetti, M. Mingari, L. Moretta
- Biology, MedicineBlood
- 15 February 2006
It is shown that MSCs sharply inhibit IL-2-induced proliferation of resting NK cells, whereas they only partially affect the proliferation of activated NK cells.
Human Dendritic Cells Activate Resting Natural Killer (NK) Cells and Are Recognized via the NKp30 Receptor by Activated NK Cells
- G. Ferlazzo, M. Tsang, L. Moretta, G. Melioli, R. Steinman, C. Münz
- BiologyThe Journal of experimental medicine
- 4 February 2002
It is suggested that DCs are able to control directly the expansion of NK cells and that the lysis of immature DCs can regulate the afferent limb of innate and adaptive immunity.
Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2.
- G. Spaggiari, A. Capobianco, H. Abdelrazik, F. Becchetti, M. Mingari, L. Moretta
- Biology, MedicineBlood
- 1 February 2008
It is demonstrated that indoleamine 2,3-dioxygenase and prostaglandin E2 represent key mediators of the MSC-induced inhibition of NK cells, which prevents the induction of effector functions, such as cytotoxic activity and cytokine production.
NKp44, A Triggering Receptor Involved in Tumor Cell Lysis by Activated Human Natural Killer Cells, Is a Novel Member of the Immunoglobulin Superfamily
Analysis of the cloned cDNA indicated that NKp44 is a novel transmembrane glycoprotein belonging to the Immunoglobulin superfamily characterized by a single extracellular V-type domain, and charged amino acid lysine in the trans Membrane region may be involved in the association ofNKp44 with the signal transducing molecule killer activating receptor–associated polypeptide (KARAP)/DAP12.
Transforming growth factor β1 inhibits expression of NKp30 and NKG2D receptors: Consequences for the NK-mediated killing of dendritic cells
- R. Castriconi, C. Cantoni, A. Moretta
- Biology, ChemistryProceedings of the National Academy of Sciences…
- 19 March 2003
It is shown that transforming growth factor β1 down-regulates the surface expression of NKp30 and in part of NKG2D but not that of other triggering receptors such as NKp46, suggesting a possible mechanism by which TGFβ1-producing dendritic cells may acquire resistance to the NK-mediated attack.