title: Mimotope mimicking epidermal growth factor receptor alleviates mononuclear cell infiltration in exocrine glands induced by muscarinic acetylcholine 3 receptor.
abstract: The muscarinic type 3 receptor (M3R) plays a pivotal role in the pathogenesis of Sjögren's syndrome (SS). Characterization of the crosstalk between M3R and EGFR has been investigated in some human malignancies. In the current study, we sought to investigate whether EGFR mimic immunization could alleviate the abnormal immune responses in an experimental SS-like model triggered by M3R peptides. After immunization with the combination of mimotope and M3R peptide, the active immunization targeting EGFR induced by the mimotope could reduce the marked infiltration of mononuclear cells, the high titer of antibodies against M3R and the accumulation of crucial pro-inflammatory cytokines in mice immunized with M3R peptide. Mechanistic analysis showed that mimotope immunization could alleviate the autoimmune response through inhibiting mitochondrion-mediated anti-apoptosis and up-regulating the FAS apoptosis pathway. These results may help to clarify the role of M3R in the pathogenesis of SS and suggested that transactivation of the EGFR signaling pathway may help M3R activate the autoimmune response in the pathogenesis of SS.
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, No.49, HuaYuan (North) Road, Beijing 100191, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Baotou Medical College, No.41, LinYin Road, Baotou 014010, PR China.
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, No.49, HuaYuan (North) Road, Beijing 100191, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital of Baotou Medical College, No.41, LinYin Road, Baotou 014010, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, No.49, HuaYuan (North) Road, Beijing 100191, PR China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Peking University Third Hospital, No.49, HuaYuan (North) Road, Beijing 100191, PR China.
authors.forename: Zhengqian
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, Peking University Third Hospital, No.49, HuaYuan (North) Road, Beijing 100191, PR China. Electronic address: liuxiangyuan2014@hotmail.com.
authors.forename: Xiangyuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology / Q000494:pharmacology*; D066246:ErbB Receptors / Q000276:immunology / Q000494:pharmacology*; D005088:Exocrine Glands / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D043587:Receptor, Muscarinic M3 / Q000276:immunology*; D012469:Salivary Glands / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology*; D014611:Vaccination
chemical_list: D000939:Epitopes; D010446:Peptide Fragments; D043587:Receptor, Muscarinic M3; C541485:EGFR protein, mouse; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Mimotope; Muscarinic type 3 receptor; Sjögren's syndrome