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Cellular mechanisms and effects of interleukin-4 receptor blockade in experimental conjunctivitis evoked by skin inflammation
Hongwei Han, … , Paul Bryce, Alexandra Hicks
Hongwei Han, … , Paul Bryce, Alexandra Hicks
Published January 10, 2023
Citation Information: JCI Insight. 2023. https://doi.org/10.1172/jci.insight.163495.
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Research In-Press Preview Dermatology Immunology

Cellular mechanisms and effects of interleukin-4 receptor blockade in experimental conjunctivitis evoked by skin inflammation

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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-4Rα) 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-4Rα 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-4Rα-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-4Rα-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.

Authors

Hongwei Han, Sheila Cummings, Kai-Ting C. Shade, Jennifer Johnson, George Qian, Joseph Gans, Srinivas Shankara, Javier M. Escobedo, Erik Zarazinski, Renee Bodinizzo, Dinesh S. Bangari, Paul Bryce, Alexandra Hicks

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