title: A critical role for thymic stromal lymphopoietin in nickel-induced allergy in mice.
abstract: Ni is the most frequent cause of contact allergy induced by metals. However, the underlying mechanism of this induction is unknown. Our previous research demonstrates that activation of dendritic cells (DCs) through p38MAPK/MKK6 is required for Ni-induced allergy in mice. In the current study, we investigated the cellular and molecular mechanisms underlying Ni-induced allergy using a mouse model that involves injecting Ni into the ear, with or without Freund's incomplete or complete adjuvants. Nickel had greater potential to cause allergic reactions compared with palladium and gold. Among the proteins expressed at higher levels in mice with Ni-induced allergy, we focused on thymic stromal lymphopoietin (TSLP), which is produced in abundance by keratinocytes. We detected increased expression of the TSLP receptor (TSLPR) in DCs from cervical lymph nodes of mice with Ni-induced allergy, suggesting that DCs in ear tissues were activated through TSLPR signaling induced by keratinocyte-derived TSLP. Furthermore, delayed-type hypersensitivity reactions in mice with Ni-induced allergy were decreased significantly by injection of a Tslp-short interfering RNA along with atelocollagen in the ear skin. These results suggest that Ni allergy may be triggered by a TSLP/TSLPR-mediated interaction between epithelial and immune cells.
authors.affiliation: Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Meinar Nur
authors.initials: MN
authors.lastname: Ashrin
authors.forename: Rieko
authors.initials: R
authors.lastname: Arakaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kondo
authors.forename: Mie
authors.initials: M
authors.lastname: Kurosawa
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.forename: Megumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009532:Nickel / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D034741:RNA, Small Interfering; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D009532:Nickel; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse