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Thymic CCL2 influences induction of T-cell tolerance.

Abstract
Thymic epithelial cells (TEC) and dendritic cells (DC) play a role in T cell development by controlling the selection of the T cell receptor repertoire. DC have been described to take up antigens in the periphery and migrate into the thymus where they mediate tolerance via deletion of autoreactive T cells, or by induction of natural regulatory T cells. Migration of DC to thymus is driven by chemokine receptors. CCL2, a major ligand for the chemokine receptor CCR2, is an inflammation-associated chemokine that induces the recruitment of immune cells in tissues. CCL2 and CCR2 are implicated in promoting experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis. We here show that CCL2 is constitutively expressed by endothelial cells and TEC in the thymus. Transgenic mice overexpressing CCL2 in the thymus showed an increased number of thymic plasmacytoid DC and pronounced impairment of T cell development. Consequently, CCL2 transgenic mice were resistant to EAE. These findings demonstrate that expression of CCL2 in thymus regulates DC homeostasis and controls development of autoreactive T cells, thus preventing development of autoimmune diseases.
AuthorsO Cédile, M Løbner, H Toft-Hansen, I Frank, A Wlodarczyk, M Irla, T Owens
JournalJournal of autoimmunity (J Autoimmun) Vol. 55 Pg. 73-85 (Dec 2014) ISSN: 1095-9157 [Electronic] England
PMID25129504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Ccl2 protein, mouse
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Receptors, CCR2
Topics
  • Animals
  • Cell Movement (genetics, immunology)
  • Chemokine CCL2 (genetics, immunology)
  • Dendritic Cells (immunology, pathology)
  • Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, pathology)
  • Immune Tolerance
  • Mice
  • Mice, Transgenic
  • Multiple Sclerosis (genetics, immunology, pathology)
  • Plasma Cells (immunology, pathology)
  • Receptors, CCR2 (genetics, immunology)
  • T-Lymphocytes (immunology, pathology)
  • Thymus Gland (immunology, pathology)

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