Type II monocytes modulate T cell-mediated central nervous system autoimmune disease

Martin S. Weber, Thomas Prod'homme, Sawsan Youssef, Shannon E. Dunn, Cynthia D. Rundle, Linda Lee, Juan C. Patarroyo, Olaf Stüve, Raymond A. Sobel, Lawrence Steinman, Scott S. Zamvil

Research output: Contribution to journalArticle

347 Scopus citations

Abstract

Treatment with glatiramer acetate (GA, copolymer-1, Copaxone), a drug approved for multiple sclerosis (MS), in a mouse model promoted development of anti-inflammatory type II monocytes, characterized by increased secretion of interleukin (IL)-10 and transforming growth factor (TGF)-β, and decreased production of IL-12 and tumor necrosis factor (TNF). This anti-inflammatory cytokine shift was associated with reduced STAT-1 signaling. Type II monocytes directed differentiation of TH2 cells and CD4+CD25 +FoxP3+ regulatory T cells (Treg) independent of antigen specificity. Type II monocyte-induced regulatory T cells specific for a foreign antigen ameliorated experimental autoimmune encephalomyelitis (EAE), indicating that neither GA specificity nor recognition of self-antigen was required for their therapeutic effect. Adoptive transfer of type II monocytes reversed EAE, suppressed TH17 cell development and promoted both TH2 differentiation and expansion of Treg cells in recipient mice. This demonstration of adoptive immunotherapy by type II monocytes identifies a central role for these cells in T cell immune modulation of autoimmunity.

Original languageEnglish (US)
Pages (from-to)935-943
Number of pages9
JournalNature medicine
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Weber, M. S., Prod'homme, T., Youssef, S., Dunn, S. E., Rundle, C. D., Lee, L., Patarroyo, J. C., Stüve, O., Sobel, R. A., Steinman, L., & Zamvil, S. S. (2007). Type II monocytes modulate T cell-mediated central nervous system autoimmune disease. Nature medicine, 13(8), 935-943. https://doi.org/10.1038/nm1620