ニッケルアレルギー惹起相におけるセマフォリン７Aの効果

Background: Metal allergy is caused by many factors, including cells, cytokines, chemokines, or the environment. Recent studies suggested semaphorin7A (Sema7A), expressed on activated T cells, is crucial to produce inflammation through α1β1 integrin on monocytes and macrophages. However, the role of Sema7A on keratinocytes in metal allergy is still unclear. In this study, we focused on keratinocytes since they are known as an important player for skin immunity, and analyzed the effect of Sema7A expressed on keratinocytes in the development of metal allergy. Materials and Methods: Mouse keratinocyte line PAM2.12 cells were treated with NiCl2 to analyze the expression of Sema7A. Ni allergy was induced in female C57BL/6J mice (6-8 weeks old) with or without Sema7A suppression to confirm if Sema7A is necessary to produce allergic reactions to NiCl2. Results: NiCl2 enhanced the expression of Sema7A in a dose and time-dependent manner after 72 hours of stimulation. PAM 2.12 produced TNF-α in response to NiCl2, and this secretion was reduced by Sema7A inhibition. In a mouse model, ear thickness, at 48 hours after NiCl2 injection, was significantly decreased by Sema7A siRNA administration. Conclusions: Sema7A is essential to produce an allergic reaction to NiCl2, especially during the effector phase. Since the interaction between Sema7A and α1β1 integrin enhances inflammation in many skin diseases, this interaction may also have possibilities to be a therapeutic target for metal allergy

Semaphorin 3A : A potential target for prevention and treatment of nickel allergy

Metal allergy is one of the typical immune disorders encountered during the application of dental/medical materials and has a highly complex pathogenic mechanism. Semaphorin 3A (Sema3A), a member of the semaphorin family, is reported to be involved in various immune disorders. However, its role in metal allergy has not been clarified yet. Herein, we show that Sema3A expression was upregulated in nickel (Ni) allergy-induced mouse ear tissue and in NiCl2-stimulated mouse keratinocytes. Moreover, Sema3A regulated tumor necrosis factor-alpha production and mitogen-activated protein kinase activation in keratinocytes. The specific deletion of Sema3A in keratinocytes did not affect immune cell infiltration but reduced edema and ear swelling; it also impeded Th1 responses to cause a slight alleviation in Ni allergy in mice. Our results demonstrate that Sema3A promotes the development of metal allergy and should be explored as a potential target for the prevention and treatment of metal allergy

Metal Allergy Mediates the Development of Oral Lichen Planus via TSLP-TSLPR Signaling

Metal allergy is a T-cell-mediated delayed type of hypersensitive reaction. The pathogenetic mechanisms underlying the allergy are unclear, although the condition has been reported to be related to oral lichen planus (OLP), despite an absence of immunological studies to support this relationship. In this study, histopathological samples of OLP patients were examined to compare the metal allergy-positive and -negative groups, with a focus on the network of epidermal keratinocytes and T cells induced by thymic stromal lymphopoietin (TSLP) and its receptor, TSLPR. Infiltration of T cells into the epithelium was revealed to be higher in the OLP lesions of metal allergy-positive patients than in those of metal allergy-negative patients. Moreover, TSLP-TSLPR signaling and TNF-α production were higher in the epithelial tissue samples of the metal allergy-positive patients than in the metal allergy-negative patients. Metal allergy is associated with both increased expressions of TSLP in keratinocytes and increased TNF-α levels in the epithelium. We propose that this would promote the accumulation of T cells at the lesion site, contributing to the formation of the disease. These results suggest that metal allergy may be an aggravating factor in the pathogenesis of OLP

金属アレルギーはTSLP-TSLPRシグナルを介して口腔扁平苔癬の発症に関与する

Metal allergy is a T-cell-mediated delayed type of hypersensitive reaction. The pathogenetic mechanisms underlying the allergy are unclear, although the condition has been reported to be related to oral lichen planus (OLP), despite an absence of immunological studies to support this relationship. In this study, histopathological samples of OLP patients were examined to compare the metal allergy-positive and -negative groups, with a focus on the network of epidermal keratinocytes and T cells induced by thymic stromal lymphopoietin (TSLP) and its receptor, TSLPR. Infiltration of T cells into the epithelium was revealed to be higher in the OLP lesions of metal allergy-positive patients than in those of metal allergy-negative patients. Moreover, TSLP-TSLPR signaling and TNF-α production were higher in the epithelial tissue samples of the metal allergy-positive patients than in the metal allergy-negative patients. Metal allergy is associated with both increased expressions of TSLP in keratinocytes and increased TNF-α levels in the epithelium. We propose that this would promote the accumulation of T cells at the lesion site, contributing to the formation of the disease. These results suggest that metal allergy may be an aggravating factor in the pathogenesis of OLP

樹状細胞はニッケルアレルギーの発症時にニッケルイオンを抗原として直接認識する

Metal hypersensitivity, a disorder of the immune system, typically manifests as contact hypersensitivity to metals during daily contact. The molecular mechanism whereby metals enter the body and cause allergic disorders remains elusive. It is thought that eluted metal ions are captured by dendritic cells (DCs) and transferred to the draining lymph nodes to activate T cells. Here, for the first time, we used a metal indicator Newport Green to locate the most common allergenic metal, nickel (Ni) ions, captured by DCs and transferred to lymph nodes. Capturing Ni ions did not affect the activity of DCs. Ni ions entered DCs and showed positive staining in keratinocytes. A time varied quantitative analysis demonstrated that at 1 h, a small amount of Ni ions was observed in the epidermal sheet. After 6 h, the number of Ni ions that entered the epidermal sheet reached a peak and remained constant for a few days and were gradually emitted 48 h later. In the cervical lymph nodes of mice, accumulation of Ni ions reached a peak within 24 h and then gradually decreased. The findings of this study will contribute to the development of effective diagnoses and treatment methods for patients allergic to Ni

Metal Allergy Mediates the Development of Oral Lichen Planus via TSLP-TSLPR Signaling

Metal allergy is a T-cell-mediated delayed type of hypersensitive reaction. The pathogenetic mechanisms underlying the allergy are unclear, although the condition has been reported to be related to oral lichen planus (OLP), despite an absence of immunological studies to support this relationship. In this study, histopathological samples of OLP patients were examined to compare the metal allergy-positive and -negative groups, with a focus on the network of epidermal keratinocytes and T cells induced by thymic stromal lymphopoietin (TSLP) and its receptor, TSLPR. Infiltration of T cells into the epithelium was revealed to be higher in the OLP lesions of metal allergy-positive patients than in those of metal allergy-negative patients. Moreover, TSLP-TSLPR signaling and TNF-α production were higher in the epithelial tissue samples of the metal allergy-positive patients than in the metal allergy-negative patients. Metal allergy is associated with both increased expressions of TSLP in keratinocytes and increased TNF-α levels in the epithelium. We propose that this would promote the accumulation of T cells at the lesion site, contributing to the formation of the disease. These results suggest that metal allergy may be an aggravating factor in the pathogenesis of OLP