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

Ji Hyeon Ju, Mi La Cho, Joo Youn Jhun, Min Jung Park, Hye Joa Oh, So Youn Min, Young Gyu Cho, Seu Yun Hwang, Seung Ki Kwok, Soo Hong Seo, Chong Hyeon Yoon, Sung Hwan Park, Ho Youn Kim

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The receptor activator of nuclear factor κB 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.

Original languageEnglish (US)
Pages (from-to)16-25
Number of pages10
JournalImmunology Letters
Volume117
Issue number1
DOIs
StatePublished - Apr 15 2008

Keywords

  • CD4+ T cells
  • Collagen-induced arthritis
  • IL-17
  • Oral tolerance
  • RANKL

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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