Dendritic cells modulated by innate immunity improve collagen-induced arthritis and induce regulatory T cells in vivo

Immunology. 2009 Jan;126(1):35-44. doi: 10.1111/j.1365-2567.2008.02875.x. Epub 2008 Aug 27.


Dendritic cells (DCs) mediate interactions between innate and specific immunity and may induce regulatory mechanisms. We investigated the effects of modulated DCs in mice with collagen-induced arthritis (CIA) and tested the responses of cells to induced naturally occurring regulatory T cells. DCs were stimulated or not with DNA or lipopolysaccharide (LPS) for 24 hr. DC maturation was assayed, and then modulated DCs were intraperitoneally injected on day 14 into DBA/1 mice to treat CIA. In addition to arthritis scores and type 2 collagen (CII) response, the induction of CD4(+) CD25(+) T cells was analysed by flow cytometry in peripheral blood and the expression of Foxp3, transforming growth factor (TGF)-beta, interleukin (IL)-10 and cytotoxic T-lymphocyte antigen (CTLA)-4 was quantified. Finally, the expression of indoleamine-2,3-dioxygenase (IDO) was assayed in DCs. In comparison with LPS-stimulated DCs, plasmid-stimulated DCs expressed lower levels of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86 molecules and secreted less IL-12p70, interferon (IFN)-gamma, IL-10 and TNF-alpha, displaying a semi-mature phenotype. Compared with non-stimulated DCs, stimulated DCs improved arthritis scores when injected after immunization, without modifying the T helper type 1 (Th1)/Th2 balance of the immune response against collagen. Stimulated DCs induced markers for regulatory T cells (Foxp3, TGF-beta1 and CTLA-4) in vivo. Only LPS-stimulated DCs expressed IDO, which may explain their better therapeutic efficacy. Regulatory mechanisms were induced using DCs modulated by innate immunity stimulators. Innate immunity mechanisms do not require the presence of the disease-causing antigen, even in T- and B-cell specific diseases. Our results have implications for the treatment of rheumatoid arthritis, an autoimmune disease whose triggering antigen has not been identified, and substantially clarify the role of regulatory T cells in CIA.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / prevention & control*
  • Cell Differentiation / immunology
  • Collagen Type II / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Forkhead Transcription Factors / biosynthesis
  • Immune Tolerance
  • Immunity, Innate
  • Immunoglobulin G / biosynthesis
  • Interleukin-10 / biosynthesis
  • Lipopolysaccharides / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Plasmids / immunology
  • Polymerase Chain Reaction / methods
  • T-Lymphocytes, Regulatory / immunology*
  • Th2 Cells / immunology
  • Transforming Growth Factor beta1 / biosynthesis


  • Collagen Type II
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunoglobulin G
  • Lipopolysaccharides
  • Transforming Growth Factor beta1
  • Interleukin-10