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Fyn regulates eosinophil infiltration into the conjunctiva by downregulating the Th2 response

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Abstract

Purpose

Under certain circumstances, fyn may serve to negatively regulate the differentiation of naïve helper T (Th) cells into Th2 cells. This study aimed to investigate whether fyn negatively regulates the development of experimental immune-mediated blepharoconjunctivitis (EC), in which Th2 cells play an important role in C57BL/6 mice.

Methods

C57BL/6 background wild-type (WT) or fyn knockout (fyn-/-) mice were subcutaneously immunized with ragweed (RW) adsorbed in aluminum hydroxide. Ten days later the mice were challenged with RW in eye drops, and 24 h after challenge, eyes, blood and spleens were harvested for histology, measurement of serum IgE, and proliferation or cytokine assays, respectively. RW-primed splenocytes from WT and fyn-/- mice were cultured in the presence of RW. Seventy-two hours later, either whole splenocytes or isolated CD4+T cells were transferred into syngeneic WT mice. Four days after the transfer, the recipient mice were challenged with RW and evaluated as described above.

Results

Infiltration of eosinophils into the conjunctiva induced by active immunization was significantly increased in fyn-/- mice relative to WT mice. Total serum IgE was also significantly higher in fyn-/- mice than in WT mice. In parallel, a higher level of IL-4 production from splenocytes was induced by concanavalin A stimulation in fyn-/- mice than in WT mice. In contrast to active immunization, transfer of whole splenocytes or separated CD4+T cells derived from WT or fyn-/- mice induced similar levels of eosinophilic infiltration in WT mice.

Conclusions

Fyn regulates infiltration of eosinophils into the conjunctiva through downregulation of Th2 responses. This negative regulation is exerted only during the induction phase of EC.

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Acknowledgements

We would like to extend our appreciation to Ms. Waka Ishida and Kazuyo Fukata for their superb technical assistance. This work was partially supported by a Kobayashi-Magobee Memorial Award and a Kochi Shinyokinko-Anshintomonokai Award.

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Authors and Affiliations

  1. Department of Ophthalmology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, 783-8505, Japan

    Atsuki Fukushima, Tomoko Yamaguchi, Akemi Ozaki & Hisayuki Ueno

  2. Medical Research Center, Kochi Medical School, Kochi University, Nankoku, Japan

    Taketoshi Taniguchi

  3. Department of Immunology, Kochi Medical School, Kochi University, Nankoku, Japan

    Keiko Udaka

Authors
  1. Atsuki Fukushima
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  2. Tomoko Yamaguchi
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  3. Akemi Ozaki
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  4. Taketoshi Taniguchi
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  5. Keiko Udaka
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  6. Hisayuki Ueno
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Corresponding author

Correspondence to Atsuki Fukushima.

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Fukushima, A., Yamaguchi, T., Ozaki, A. et al. Fyn regulates eosinophil infiltration into the conjunctiva by downregulating the Th2 response. Graefe's Arch Clin Exp Ophthalmo 243, 1043–1049 (2005). https://doi.org/10.1007/s00417-005-1158-1

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  • DOI: https://doi.org/10.1007/s00417-005-1158-1

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