Abstract
Chromium (Cr) causes delayed-type hypersensitivity reactions possibly mediated by accumulating T cells into allergic inflamed skin, which are called irritants or allergic contact dermatitis. However, accumulating T cells during development of metal allergy are poorly characterized because a suitable animal model is not available. This study aimed to elucidate the skewing of T-cell receptor (TCR) repertoire and cytokine profiles in accumulated T cells in inflamed skin during elucidation of Cr allergy. A novel model of Cr allergy was induced by two sensitizations of Cr plus lipopolysaccharide solution into mouse groin followed by single Cr challenge into the footpad. TCR repertoires and nucleotide sequences of complementary determining region 3 were assessed in accumulated T cells from inflamed skin. Cytokine expression profiles and T-cell phenotypes were determined by qPCR. CD3+CD4+ T cells accumulated in allergic footpads and produced increased T helper 1 (Th1) type cytokines, Fas, and Fas ligand in the footpads after challenge, suggesting CD4+ Th1 cells locally expanded in response to Cr. Accumulated T cells included natural killer (NK) T cells and Cr-specific T cells with VA11-1/VB14-1 usage, suggesting metal-specific T cells driven by invariant NKT cells might contribute to the pathogenesis of Cr allergy.
Highlights
Metal allergy is categorized as a delayed-type hypersensitivity (DTH) reaction, and may be caused by metal ions released from dental materials, jewelry, and coins [1]
This study demonstrated the successful establishment of a murine model of Cr-induced ICD and allergic contact dermatitis (ACD) with appropriate pathology
We observed that allergen specific T cells used a specific T-cell receptor (TCR) repertoire in Cr-induced ACD mice
Summary
Metal allergy is categorized as a delayed-type hypersensitivity (DTH) reaction, and may be caused by metal ions released from dental materials, jewelry, and coins [1]. The number of patients with metal allergy has increased because metal is increasingly used for jewelry, surgical instruments, and dental restorations [1]. Cr hypersensitivity is one of the major occupational metal skin diseases especially in cement workers [2,3]. Cr hypersensitivity is common in the general population with a prevalence of approximately 0.5% [4,5], whereas the prevalence in cement workers is approximately 4.5% [4,6]. Skin exposure to Cr produces both irritant (ICD) and allergic contact dermatitis (ACD). The irritant reaction does not require previous sensitization, and both types of contact dermatitis, despite their induction by different mechanisms, have not been differentiated by macroscopic appearance [8]
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