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 in producing 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 in producing allergic reactions to NiCl₂.
Results: NiCl₂ enhanced the expression of Sema7A in a dose and time-dependent manner after 72 hours of stimulation. PAM2.12 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, significantly decreased by Sema7A siRNA administration.
Conclusions: Sema7A is essential in producing 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.