Neutralization of IFN-inducible protein 10/CXCL10 exacerbates experimental autoimmune encephalomyelitis

Chigusa Nakajima, Takao Mukai, Nobuya Yamaguchi, Yasunari Morimoto, Woong Ryeon Park, Masayuki Iwasaki, Ping Gao, Shiro Ono, Hiromi Fujiwara, Toshiyuki Hamaoka

Research output: Contribution to journalArticle

Abstract

We examined the effect of a monoclonal antibody (mAb) against interferon (IFN)-inducible protein 10 (IP-10)/CXCL10 on the development of experimental autoimmune encephalomyelitis (EAE) in rats induced by injecting xenogeneic brain homogenates into footpads. Treatment with neutralizing mAb against CXCL10 exacerbated EAE with increased infiltrating CD4+ cells in the central nervous system. Furthermore, the exacerbation by the mAb treatment was accompanied by less enlarged draining popliteal lymph nodes (LN) in parallel with cell number compared with those of EAE rats treated with control mAb, whereas other lymphoid organs such as the spleen and thymus were not significantly different between rats treated with anti-CXCL10 and the control mAb. Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats. Induction of the third CXCR3 ligand, CXCL11/I-TAC was not seen in the draining LN, whereas all three CXCR3 ligands and CXCR3 itself were markedly detected in the spinal cords following the development of EAE. These findings suggest that CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN.

Original languageEnglish (US)
Pages (from-to)1784-1791
Number of pages8
JournalEuropean Journal of Immunology
Volume32
Issue number6
DOIs
StatePublished - 2002

Keywords

  • Chemokine
  • Experimental autoimmune encephalomyelitis
  • Lymph node
  • Spleen
  • Th1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Nakajima, C., Mukai, T., Yamaguchi, N., Morimoto, Y., Park, W. R., Iwasaki, M., Gao, P., Ono, S., Fujiwara, H., & Hamaoka, T. (2002). Neutralization of IFN-inducible protein 10/CXCL10 exacerbates experimental autoimmune encephalomyelitis. European Journal of Immunology, 32(6), 1784-1791. https://doi.org/10.1002/1521-4141(200206)32:6<1784::AID-IMMU1784>3.0.CO;2-R