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However, treatments that target inflammatory mediators or immune cells are often unsatisfying in relieving the stubborn itch symptom. This suggests that additional mechanisms are responsible for ocular itch in ACJ. In this study, we aim to determine the role of neuronal Fc\u03b5RIa in allergic ocular itch.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Calcium imaging was applied to observe the effect of IgE-immune complex in trigeminal neurons. Genomic<jats:italic>Fc\u03b5RIa<\/jats:italic>knockout mice and adeno-associated virus (AAV) mediated sensory neuron<jats:italic>Fc\u03b5RIa<\/jats:italic>knockdown mice were used in conjunction with behavioral tests to determine ocular itch. In addition, immunohistochemistry, Western blot and quantitative RT-PCR were used for in vitro experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that Fc\u03b5RI\u03b1 was expressed in a subpopulation of conjunctiva sensory neurons. IgE-IC directly activated trigeminal neurons and evoked acute ocular itch without detectible conjunctival inflammation. These effects were attenuated in both a global<jats:italic>Fc\u03b5RIa<\/jats:italic>-knockout mice and after sensory neuronal-specific<jats:italic>Fc\u03b5RIa<\/jats:italic>-knockdown in the mouse trigeminal ganglion. In an ovalbumin (OVA) induced murine ACJ model, Fc\u03b5RI\u03b1 was found upregulated in conjunctiva-innervating CGRP+\u2009sensory neurons. Sensory neuronal-specific knockdown of<jats:italic>Fc\u03b5RIa<\/jats:italic>significantly alleviated ocular itch in the ACJ mice without affecting the immune cell infiltration and mast cell activation in conjunctiva. Although Fc\u03b5RI\u03b1 mRNA expression was not increased by IgE in dissociated trigeminal ganglion neurons, Fc\u03b5RI\u03b1 protein level was enhanced by IgE in a cycloheximide-resistance manner, with concordant enhancement of neuronal responses to IgE-IC. In addition, incremental sensitization gradually enhanced the expression of Fc\u03b5RI\u03b1 in small-sized trigeminal neurons and aggravated OVA induced ocular itch.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrates that Fc\u03b5RI\u03b1 in pruriceptive neurons directly mediates IgE-IC evoked itch and plays an important role in ocular itch in a mouse model of ACJ. These findings reveal another axis of neuroimmune interaction in allergic itch condition independent to the classical IgE-mast cell pathway, and might suggest novel therapeutic strategies for the treatment of pruritus in ACJ and other immune-related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12974-022-02417-x","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T13:03:20Z","timestamp":1645621400000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Neuronal Fc\u03b5RI\u03b1 directly mediates ocular itch via IgE-immune complex in a mouse model of allergic conjunctivitis"],"prefix":"10.1186","volume":"19","author":[{"given":"Huan","family":"Cui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yehong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1346-6961","authenticated-orcid":false,"given":"Chao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"2417_CR1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/ACI.0b013e32834a9676","volume":"11","author":"N Rosario","year":"2011","unstructured":"Rosario N, Bielory L. 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