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Activation of tumour-necrosis factor-related apoptosis-inducing ligand receptor enhances the severity of murine allergic conjunctivitis
  1. T Sumi1,
  2. W Ishida1,
  3. K Okumura2,
  4. H Yagita2,
  5. A Fukushima1
  1. 1
    Department of Ophthalmology and Visual Science, Kochi Medical School
  2. 2
    Department of Immunology, Juntendo University School of Medicine
  1. Dr A Fukushima, Department of Ophthalmology, Kochi Medical School, Kohasu, Oko-cho, Nankoku-city 783-8505, Japan; fukusima{at}


Background/aims: Tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) plays a role in the development of allergic asthma. The study aimed to determine whether TRAIL also participates in the development of experimental allergic conjunctivitis (EC), another allergic disease model.

Methods: EC was induced in BALB/c mice by active immunisation with ragweed (RW) followed by RW challenge. To investigate whether TRAIL in the conjunctiva plays a role in the development of EC, conjunctival TRAIL expression in EC-developing mice was evaluated by immunohistochemistry. Additionally, the effect of subconjunctival injection of recombinant TRAIL on conjunctival inflammation was examined. To investigate whether TRAIL expressed in systemic immunocompetent cells plays a role in the development of EC, anti-TRAIL blocking Ab or anti-TRAIL receptor agonistic Ab was intraperitoneally injected into EC-developing mice, and conjunctival eosinophil infiltration was evaluated.

Results: Conjunctival TRAIL expression was not increased by EC induction. Moreover, subconjunctival injection of TRAIL protein in naïve mice did not induce conjunctival inflammation. Thus, TRAIL in the conjunctiva is less likely to participate in the development of EC. Systemic treatment with anti-TRAIL blocking Ab in EC-developing mice did not affect the severity of EC. However, systemic treatment during the induction phase of EC with an agonistic Ab for the TRAIL receptor significantly augmented the severity of EC and increased Ag-recall splenocyte IFN-γ production in vitro.

Conclusions: These results indicate that TRAIL receptor-expressing cells in lymphoid organ participate in the development of EC.

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  • Competing interests: None.

  • Funding: This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (AF).

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