Neuronal FcεRIα directly mediates ocular itch via IgE-immune complex in a mouse model of allergic conjunctivitis

• DOI: 10.1186/s12974-022-02417-x
• Publication Date: 2022-02-23T13:03:20Z
• Authors: Huan Cui; Fan Liu; Yehong Fang; Tao Wang; Bo Yuan; Chao Ma
• Keywords: Trigeminal ganglion; Knockout mouse

Classical understanding of allergic conjunctivitis (ACJ) suggests that ocular itch results from a mast cell-dependent inflammatory process. However, treatments target mediators or immune cells are often unsatisfying in relieving the stubborn symptom. This additional mechanisms responsible for ACJ. In this study, we aim to determine role neuronal FcεRIa itch.Calcium imaging was applied observe effect IgE-immune complex trigeminal neurons. Genomic knockout mice and adeno-associated virus (AAV) mediated sensory neuron knockdown were used conjunction with behavioral tests itch. addition, immunohistochemistry, Western blot quantitative RT-PCR vitro experiments.We found FcεRIα expressed subpopulation conjunctiva IgE-IC directly activated neurons evoked acute without detectible conjunctival inflammation. These effects attenuated both global FcεRIa-knockout after neuronal-specific FcεRIa-knockdown mouse ganglion. an ovalbumin (OVA) induced murine ACJ model, upregulated conjunctiva-innervating CGRP+ Sensory significantly alleviated affecting cell infiltration activation conjunctiva. Although mRNA expression not increased by IgE dissociated ganglion neurons, protein level enhanced cycloheximide-resistance manner, concordant enhancement responses IgE-IC. incremental sensitization gradually small-sized aggravated OVA itch.Our study demonstrates pruriceptive mediates plays important model findings reveal another axis neuroimmune interaction condition independent classical IgE-mast pathway, might suggest novel therapeutic strategies treatment pruritus other immune-related disorders.