Your browser doesn't support javascript.
loading
miR-155 Upregulation in Dendritic Cells Is Sufficient To Break Tolerance In Vivo by Negatively Regulating SHIP1.
Lind, Evan F; Millar, Douglas G; Dissanayake, Dilan; Savage, Jonathan C; Grimshaw, Natasha K; Kerr, William G; Ohashi, Pamela S.
Afiliación
  • Lind EF; Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2C1, Canada; Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, OR 97239;
  • Millar DG; Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2C1, Canada;
  • Dissanayake D; Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2C1, Canada; Department of Immunology, University of Toronto, University Health Network, Toronto, Ontario M5G 2C1, Canada;
  • Savage JC; Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, OR 97239;
  • Grimshaw NK; Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2C1, Canada;
  • Kerr WG; Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210; and Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, NY 13210.
  • Ohashi PS; Campbell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2C1, Canada; Department of Immunology, University of Toronto, University Health Network, Toronto, Ontario M5G 2C1, Canada; pohashi@uhnres.utoronto.ca.
J Immunol ; 195(10): 4632-40, 2015 Nov 15.
Article en En | MEDLINE | ID: mdl-26447227
TLR-induced maturation of dendritic cells (DCs) leads to the production of proinflammatory cytokines as well as the upregulation of various molecules involved in T cell activation. These are believed to be the critical events that account for the induction of the adaptive immune response. In this study, we have examined the role of miR-155 in DC function and the induction of immunity. Using a model in which the transfer of self-Ag-pulsed, TLR-matured DCs can induce a functional CD8 T cell response and autoimmunity, we find that DCs lacking miR-155 have an impaired ability to break immune tolerance. Importantly, transfer of self- Ag-pulsed DCs overexpressing miR-155 was sufficient to break tolerance in the absence of TLR stimuli. Although these unstimulated DCs induced T cell function in vivo, there was no evidence for the upregulation of costimulatory ligands or cytokine secretion. Further analysis showed that miR-155 influenced the level of the phosphatase SHIP1 in DCs and that the lack of SHIP1 in DCs was sufficient to break T cell tolerance in vivo, again in the absence of TLR-induced DC maturation. Our study demonstrates that the overexpression of miR-155 in DCs is a critical event that is alone sufficient to break self-tolerance and promote a CD8-mediated autoimmune response in vivo. This process is independent of the induction of conventional DC maturation markers, indicating that miR-155 regulation of SHIP represents a unique axis that regulates DC function in vivo.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Dendríticas / Monoéster Fosfórico Hidrolasas / MicroARNs / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Células Dendríticas / Monoéster Fosfórico Hidrolasas / MicroARNs / Tolerancia Inmunológica Límite: Animals Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article