title: Neuronal Fc-epsilon receptor I contributes to antigen-evoked pruritus in a murine model of ocular allergy.
abstract: Pruritus is the major symptom of ocular allergy but currently available treatments are often ineffective. Previous studies demonstrated that subpopulations of primary sensory neurons express Fc receptors and may contribute to antigen-specific pain. We investigated the role of neuronal Fc-epsilon Receptor I (FcεRI) in allergic ocular pruritus. Ovalbumin (OVA) was used as allergen together with alum adjuvant (OVA+alum) to produce a mouse model of ocular allergy with a significant elevation in the serum levels of both antigen-specific IgE and IgG. Mice sensitized by OVA without alum only induced elevation of serum IgG but not IgE. Scratching behavior toward the eyes with the hindlimb was used as an indicator of ocular itch. Topical OVA challenging to the eye dose-dependently induced scratching toward the eye in the OVA+alum sensitized mice, but not those sensitized by OVA only. The antigen-induced scratching was largely abolished by topical application of the blocking antibody to FcεRIα, but was only partially alleviated by pretreatment of mast cell stabilizer or histamine I receptor antagonist. The expression of FcεRI was detected in subpopulations of trigeminal ganglion (TG) neurons including those expressing pruriceptive markers and innervating the conjunctiva in the naïve mice. Moreover, FcεRI was found significantly upregulated in small-sized TG neurons in the OVA+alum sensitized mice. In acutely dissociated TG neurons, IgE-immune complex (IC), but not the antibody or antigen alone, induced intracellular calcium increase. The neuronal responses to IgE-IC could be specifically blocked by pre-application of a siRNA for FcεRIα. Our results indicate that FcεRI expressed on peripheral nociceptive neurons in the TG may be directly activated by IgE-IC and contribute to allergic ocular pruritus. This study may suggest a novel mechanism for the development of pathological itch in allergic diseases.
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Lubin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Naze
authors.initials: N
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Yikuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address: machao@ibms.cams.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
mesh_terms: D000534:Alum Compounds; D000818:Animals; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000276:immunology / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D010047:Ovalbumin; D011537:Pruritus / Q000276:immunology / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*
chemical_list: D000534:Alum Compounds; D017455:Receptors, IgE; C446402:ovalbumin-alum; D010047:Ovalbumin
keywords: Fc-epsilon receptor type I; IgE immune complex; Itch; Nociceptive neurons; Trigeminal ganglion