title: Myeloid dendritic cells stimulated by thymic stromal lymphopoietin promote Th2 immune responses and the pathogenesis of oral lichen planus.
abstract: Oral lichen planus (OLP) is a chronic inflammatory disease characterized by subepithelial T-cell infiltration. Recent studies reported that specific T helper (Th) subsets, especially Th2 cells, are involved in the pathogenesis of OLP. Thymic stromal lymphopoietin (TSLP) is mainly secreted by epithelial cells and potently activates myeloid dendritic cells (mDCs) to induce Th2-mediated inflammation. Here, we investigated the expression of TSLP and related molecules in OLP. Buccal mucosa specimens from patients with OLP, hyperkeratosis, and ulcer were analyzed by immunohistochemistry for expression of TSLP, its receptor (TSLPR), and inflammatory cells. TSLP was detected in/around the epithelium of patients with OLP and hyperkeratosis, whereas TSLPR, CD11c (mDC), and GATA3 (Th2) were strongly expressed in the subepithelial layer only in OLP patients. Double immunofluorescence staining showed that TSLPR expression mainly co-localized with CD11c. Moreover, the number of CD11c- and GATA-3 positive cells was correlated in OLP patients. In lesions selectively extracted by laser microdissection, the mRNA expression of Th2 (IL-4, MDC, TARC, GATA3)- and Th17 (IL-17, RORγt)-related molecules in OLP patients was significantly higher than in other groups. These results suggest that CD11c+ mDCs expressing TSLPR contribute to aberrant Th2 immune responses and the pathogenesis of OLP via TSLP stimulation.
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Yamauchi
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.|OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Masafumi
authors.identifier: http://orcid.org/0000-0003-2911-2244
authors.initials: M
authors.lastname: Moriyama
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Jun-Nosuke
authors.initials: JN
authors.lastname: Hayashida
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maehara
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Kubota
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Furukawa
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ohta
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Sakamoto
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D039521:CD11c Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D017676:Lichen Planus, Oral / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D039521:CD11c Antigen; C498762:CRLF2 protein, human; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin