title: ILT3.Fc inhibits the production of exosomes containing inflammatory microRNA in supernatants of alloactivated T cells.
abstract: Immune activation needs to be tightly regulated to control immune-mediated tissue damage. Inhibitory pathways serve to terminate an immune response and resolve inflammation. Persistent exposure to antigens can drive development of adaptive regulatory cells. Similarly exposure of activated T cells to the recombinant ILT3-Fc molecule during priming triggers the differentiation of CD8 T suppressor cells and the induction of CD4 T helper anergy. Ts express high levels of immunoregulatory signature genes together with low levels of microRNA which control their function. Analysis of microRNA contained by exosomes from cultures in which T cells were alloactivated in the presence or absence of ILT3.Fc, demonstrated that this agent inhibits the release of inflammatory microRNA. The source of such inflammatory microRNA was found to reside in alloactivated CD4 T cells, since exosomes from MLC primed CD4 T cells were shown to diminish the suppressive activity of ILT3-Fc-induced CD8(+) Ts at high effector to suppressor T cell ratios. This indicates that inflammatory exosomes can swing the balance between effector and regulatory T cells in favor of immunity. These data suggest that isolation and characterization of micro-RNA containing exosomes in patients' circulation may be of use for treatment, prevention and monitoring of immune activation.
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Sophey
authors.initials: S
authors.lastname: Ho
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Zhuoru
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Muyang
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Vasilescu
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Raphael A
authors.initials: RA
authors.lastname: Clynes
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: George
authors.initials: G
authors.lastname: Vlad
authors.affiliation: Department of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA. Electronic address: ns20@columbia.edu.
authors.forename: Nicole
authors.initials: N
authors.lastname: Suciu-Foca
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D055354:Exosomes / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic; D015398:Signal Transduction
chemical_list: D007141:Immunoglobulin Fc Fragments; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic
keywords: CD8 T suppressor cells; Exosomes; MicroRNA