Transgenic expression of CCL2 in the central nervous system prevents experimental autoimmune encephalomyelitis

Adam Elhofy, Jintang Wang, Mari Tani, Brian T. Fife, Kevin J. Kennedy, Jami Bennett, Deren Huang, Richard M. Ransohoff, William J. Karpus

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

CC chemokine ligand 2 (CCL2)/monocyte chetnotactic protein-1, a member of the CC chemokine family, is a chemoattractant for monocytes and T cells through interaction with its receptor CCR2. In the present study, we examined a T helper cell type 1 (Th1)-dependent disease, proteolipid protein-induced experimental autoimmune encephalomyelitis, in a transgenic mouse line that constitutively expressed low levels of CCL2 in the central nervous system (CNS) under control of the astrocyte-specific glial fibrillary acidic protein promoter. CCL2 transgenic mice developed significantly milder clinical disease than littermate controls. As determined by flow cytometry, mononuclear cell infiltrates in the CNS tissues of CCL2 transgenic and littermate-control mice contained equal numbers of CD4 + and CD8 + T cells, and the CCL2 transgenic mice showed an enhanced number of CNS-infiltrating monocytes. CNS antigen-specific T cells from CCL2 transgenic mice produced markedly less interferon-γ. Overexpression of CCL2 in the CNS resulted in decreased interleukin-12 receptor expression by antigen-specific T cells. Collectively, these results indicate that sustained, tissue-specific expression of CCL2 in vivo down-regulates the Th1 autoimmune response, culminating in milder clinical disease.

Original languageEnglish (US)
Pages (from-to)229-237
Number of pages9
JournalJournal of Leukocyte Biology
Volume77
Issue number2
DOIs
StatePublished - Feb 2005
Externally publishedYes

Keywords

  • Chemokines
  • EAE
  • IL-12R
  • MCP-1
  • Multiple sclerosis

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