A non-peptide CCR5 antagonist inhibits collagen-induced arthritis by modulating T cell migration without affecting anti-collagen T cell responses

Yi Fu Yang, Takao Mukai, Ping Gao, Nobuya Yamaguchi, Shiro Ono, Hiroshi Iwaki, Satoshi Obika, Takeshi Imanishi, Takahiro Tsujimura, Toshiyuki Hamaoka, Hiromi Fujiwara

Research output: Contribution to journalArticle

Abstract

The chemokine receptors CCR5 and CXCR3 have been implicated as playing a central role in directing a Th1 inflammatory response. Here, we investigated whether a synthetic CCR5 antagonist affects the process of T cell migration to sites of inflammation. Immunization of DBA/1 mice with type II collagen resulted in typical arthritis, which is associated with cellular infiltration. Treatment with a CCR5 antagonist strikingly affected the development of arthritis by reducing both incidence and severity of disease. There was no substantial difference between collagen-immunized mice with and without antagonist treatment in the induction of anti-collagen T cell responses and the capacity to produce IL-12. This endogenous IL-12 functioned to induce comparable levels of CCR5 in these two immunized groups of T cells. Whereas a massive infiltration of inflammatory cells including CCR5+ T cells occurred in the joints of mice immunized without antagonist, cellular infiltration in the antagonist-treated group was only marginal. These results indicate that administration of a CCR5 antagonist inhibits the development of arthritis not by affecting the generation of collagen-sensitized T cells but by interfering with their migration to joint lesions.

Original languageEnglish (US)
Pages (from-to)2124-2132
Number of pages9
JournalEuropean Journal of Immunology
Volume32
Issue number8
DOIs
StatePublished - Aug 2002

Keywords

  • Chemokine
  • Chemokine receptor
  • IL-12
  • Rheumatoid arthritis
  • T cell migration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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