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ludc web

Lena Eliasson

Principal investigator

ludc web

CD46 Activation Regulates miR-150-Mediated Control of GLUT1 Expression and Cytokine Secretion in Human CD4+ T Cells.

Author

  • Ben King
  • Jonathan Esguerra
  • Ewelina Golec
  • Lena Eliasson
  • Claudia Kemper
  • Anna Blom

Summary, in English

CD46 is a cell surface complement inhibitor widely expressed in human tissues, in contrast to mice, where expression is limited to the testes. In humans, it has been identified as an important T cell costimulatory receptor, and patients deficient in CD46 or its endogenous ligands are unable to mount effective Th1 T cell responses. Stimulation of human CD4(+) T cells with CD3 and CD46 also leads to the differentiation of a "switched" Th1 population, which shuts down IFN-γ secretion and upregulates IL-10 and is thought to be important for negative feedback regulation of the Th1 response. In the present study, we show that CD46 costimulation leads to amplified microRNA (miR) expression changes in human CD4(+) T cells, with associated increases in activation more potent than those mediated by the "classic" costimulator CD28. Blockade of cell surface CD46 inhibited CD28-mediated costimulation, identifying autocrine CD46 signaling as downstream of CD28. We also identify a downregulation of miR-150 in CD46-costimulated T cells and identify the glucose transporter 1 encoding transcript SLC2A1 as a target of miR-150 regulation, connecting miR-150 with modulation of glucose uptake. We also investigated microRNA expression profiles of CD46-induced switched IL-10-secreting Th1 T cells and found increased expression of miR-150, compared with IFN-γ-secreting Th1 cells. Knockdown of miR-150 led to a reduction in IL-10 but not IFN-γ. CD46 therefore controls both Th1 activation and regulation via a miR-150-dependent mechanism.

Department/s

  • Protein Chemistry, Malmö
  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Department of Translational Medicine

Publishing year

2016-01-08

Language

English

Pages

1636-1645

Publication/Series

Journal of immunology (Baltimore, Md. : 1950)

Volume

196

Issue

4

Document type

Journal article

Publisher

American Association of Immunologists

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Protein Chemistry, Malmö
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1550-6606