Oral administration of type-II collagen suppresses IL-17-associated RANKL expression of CD4+ T cells in collagen-induced arthritis

Immunol Lett. 2008 Apr 15;117(1):16-25. doi: 10.1016/j.imlet.2007.09.011. Epub 2007 Oct 22.

Abstract

The receptor activator of nuclear factor kappaB ligand (RANKL) is an osteoclastogenic mediator, which is mainly expressed by stromal cells and osteoblast. However, T cells can also be an important provider for RANKL in special condition such as autoimmune arthritis. We examined the RANKL expression of hyporesponsive CD4+ T cells induced by oral feeding with type II collagen in collagen-induced arthritis (CIA) mice. The potential of RANKL expression in CD4+ T cells was downregulated in tolerance, as compared with CIA. One of possible explanations for this phenomenon is that CII-specific T cell activation was intrinsically impaired in oral tolerance, which caused suppression of RANKL expression of CD4+ T cells. We also investigated the extrinsic role of cytokine in this process. IL-17, well-known pro-inflammatory cytokine was upregulated in CIA and downregulated in tolerance. IL-17 had a potential to stimulate T cells to express RANKL in dose-dependent manner. IL-17-associated RANKL expression of CD4+ T cells was downregulated in oral tolerance, suggesting that the induction of tolerance ameliorates IL-17-induced RANKL expression of T cells in murine CIA. We also discovered that CIA - T cells could enhance osteoclastogenesis but not oral tolerance - T cells. Oral tolerance might be promising therapeutic option in viewpoints of modulating autoreactivity of CII which can induce not only IL-17 production but also RANKL expression in CD4+ T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Collagen Type II / administration & dosage*
  • Gene Expression
  • Immune Tolerance*
  • Interleukin-10 / metabolism
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / metabolism*
  • Interleukin-17 / pharmacology
  • Joints / metabolism
  • Joints / pathology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Osteoclasts / cytology
  • Osteoprotegerin / biosynthesis
  • RANK Ligand / biosynthesis*
  • RANK Ligand / genetics
  • Receptor Activator of Nuclear Factor-kappa B / biosynthesis

Substances

  • CD3 Complex
  • Collagen Type II
  • Interleukin-17
  • Osteoprotegerin
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Interleukin-10