A Novel Epithelial Proallergic Cytokine IL‐33 Serves As A Biomarker For Ocular Allergic Inflammation

Abstract

PurposeTo explore a novel role of interleukin (IL)‐33 in Th2‐dominant allergic inflammation on ocular surface.MethodsIL‐33 and its signaling molecules were evaluated in patients with atopic conjunctivitis and in experimental allergic conjunctivitis (EAC) mice induced by short ragweed (SRW). Human corneal epithelial cells (HCECs) were cultured for IL‐33 regulation.ResultsIL‐33 and ST2 were highly detected in conjunctival impression cytology samples from atopic conjunctivitis patients. In the SRW‐induced EAC mice, IL‐33 and ST2 transcripts and immunoreactivity significantly increased in the corneal and conjunctival epithelia with largely infiltrated CD11c+/OX40L+ dendritic cells. Th2 cell infiltration was evidenced by increased transcripts and immunoreactivity of CD4, IL‐4, IL‐5 and IL‐13 in the conjunctiva, with increased expression of OX40, STAT6 and GATA3. In culture model, IL‐33 was dramatically stimulated in HCECs exposed to microbial ligands through toll‐like receptor (TLR) and NF‐kB pathways.ConclusionsOur findings demonstrate an important role of mucosal epithelial cells in initiating Th2‐dominant ocular allergic inflammation by IL‐33‐ST2 signaling pathways.