Cellular mechanisms and effects of interleukin-4 receptor alpha blockade in a novel murine model of conjunctivitis evoked by skin inflammation

Abstract Ocular surface diseases, including conjunctivitis, are recognized as a common comorbidity in atopic dermatitis (AD) and also occur at an increased frequency in AD patients treated with biologics targeting interleukin-4 receptor alpha (IL-4Ra) or IL-13. However, the inflammatory mechanisms underlying this pathology are unknown. Here, we developed a novel mouse model of skin inflammation-evoked conjunctivitis and showed that it is dependent on CD4+ T cells and basophils. Blockade of IL-4Ra partially attenuated conjunctivitis development, downregulated basophil activation and led to a reduction in expression of genes related to type 2 cytokine responses. Together, these data suggest that an IL-4Ra-basophil axis plays a role in the development of murine allergic conjunctivitis. Interestingly, we found a significant augmentation of a number of genes that encode tear proteins and enzymes in anti-IL-4Ra-treated mice, which may underlie the partial efficacy in this model and may represent candidate mediators of the increased frequency of conjunctivitis following dupilumab in AD patients.