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

Abstract

Ocular surface diseases, including conjunctivitis, are recognized as a common comorbidity in atopic dermatitis (AD) and 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.

Atopic dermatitis and ocular allergy: common mechanisms and uncommon questions

“…The role of Th2 signaling in augmenting cutaneous inflammation–associated conjunctivitis was recently shown using mouse model [52 ▪▪ ]. In this model, mice were exposed to ovalbumin allergen in the presence of MC903 (a vitamin D analog) to induce AD-like skin inflammation.…”

A Review of Dupilumab in the Treatment of Atopic Dermatitis in Infants and Children

“…The adverse effects of conjunctivitis observed in the clinical trial using dupilumab treatment may be attributable to either insufficient inhibition of IL-4Rα or to the alternate pathway through which Th2 inflammation is activated. 47 , 48 …”

“…The adverse effects of conjunctivitis observed in the clinical trial using dupilumab treatment may be attributable to either insufficient inhibition of IL-4Rα or to the alternate pathway through which Th2 inflammation is activated. 47,48 Dupilumab Reduces Patients' Disease Burden and Improve Quality of Life Atopic dermatitis has a profound effect on the patient's quality of life, and its chronic and recurrent nature increases the financial burden on the patient's family. In infants and younger pediatric patients, the effect of sleep quality on the lives https://doi.org/10.2147/DDDT.S457761…”