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Intravenous transfer of apoptotic cell-treated dendritic cells leads to immune tolerance by blocking Th17 cell activity.

Abstract
Apoptotic cell-induced tolerogenic dendritic cells (DCs) play an important role in induction of peripheral tolerance in vivo; however, the mechanisms of immune tolerance induced by these DCs are poorly understood. Here we show that treatment of apoptotic cells modulates expression of inflammation- and tolerance-associated molecules including Gr-1, B220, CD205 and galectin-1 on bone marrow-derived DCs. In addition, apoptotic cell-treated DCs suppress secretion of cytokines produced by Th17 cells. Our data also demonstrate that i.v. transfer of apoptotic cell-treated DCs blocks EAE development and down-regulates production of inflammatory cytokines such as IL-17A and IL-17F in CD4+ T cells. These results suggest that apoptotic cell-treated DCs may inhibit activity of Th17 cells via down-regulation of inflammatory cytokine production, thereby affecting EAE development in vivo. Our results reveal a potential mechanism of immune tolerance mediated by apoptotic cell-treated DCs and the possible use of apoptotic cell-treated DCs to treat autoimmune diseases such as MS/EAE.
AuthorsFang Zhou, Elisabetta Lauretti, Antonio di Meco, Bogoljub Ciric, Patricia Gonnella, Guang-Xian Zhang, Abdolmohamad Rostami
JournalImmunobiology (Immunobiology) Vol. 218 Issue 8 Pg. 1069-76 (Aug 2013) ISSN: 1878-3279 [Electronic] Netherlands
PMID23587571 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier GmbH. All rights reserved.
Chemical References
  • Antigens, CD
  • Cytokines
  • DEC-205 receptor
  • Galectin 1
  • Gr-1 protein, mouse
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Cell Surface
  • Receptors, Chemokine
  • myelin oligodendrocyte glycoprotein (35-55)
  • Leukocyte Common Antigens
Topics
  • Animals
  • Antigens, CD (biosynthesis)
  • Apoptosis (immunology)
  • Bone Marrow Cells (immunology)
  • Cell Differentiation (immunology)
  • Cells, Cultured
  • Cytokines (biosynthesis)
  • Dendritic Cells (immunology, metabolism)
  • Encephalomyelitis, Autoimmune, Experimental (immunology, therapy)
  • Female
  • Galectin 1 (biosynthesis)
  • Immune Tolerance (immunology)
  • Immunotherapy
  • Lectins, C-Type (biosynthesis)
  • Leukocyte Common Antigens (biosynthesis)
  • Mice
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • Myelin-Oligodendrocyte Glycoprotein (administration & dosage, immunology)
  • Peptide Fragments (administration & dosage, immunology)
  • Receptors, Cell Surface (biosynthesis)
  • Receptors, Chemokine (biosynthesis)
  • Th17 Cells (immunology, metabolism)

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