Contributions of Interleukin-33 and TSLP in a papain-soaked contact lens-induced mouse conjunctival inflammation model.

INTRODUCTION

Pathological changes of severe chronic allergic conjunctivitis are driven not only via acquired immunity but also via innate immunity. Type 2 immune response-initiating cytokines may play some roles as innate immunity-dependent components of the ocular surface inflammation. To investigate the involvement of type 2 immune response-initiating cytokines in innate immunity-dependent, papain-induced conjunctival inflammation model using IL-25-, IL-33-, and TSLP receptor (TSLPR)-knockout (KO) mice with reference to basophils and ILC2.

METHODS

Papain-soaked contact lenses (papain-CLs) were installed in the conjunctival sacs of C57BL/6-IL-25 KO, IL-33 KO, TSLPR KO, Rag2 KO, Bas-TRECK, and wild-type mice and their eyes were sampled at day 5. The eosinophil and basophil infiltration in papain-CL model was evaluated histologically and cytokine expression was examined. To clarify the roles of basophils and ILC2, basophil/ILC2-depletion experiments were carried out.

RESULTS

Papain-induced conjunctival inflammation exhibited eosinophil infiltration and upregulation of Th2 cytokine expression. Reduction of eosinophil and basophil infiltration and attenuated Th2 cytokine expression were observed in the papain-CL model using IL-33 KO and TSLPR KO mice. Depletion of basophils or ILC2s in the conjunctivae of the papain-CL model reduced eosinophil infiltration.

CONCLUSIONS

Innate immunity-driven type 2 immune responses of the ocular surface are dependent on IL-33, TSLP, basophils, and ILC2. These components may be possible therapeutic targets for refractory allergic keratoconjunctivitis.