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

Abstract

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.

The association between skin allergy testing and oral squamous cell carcinoma in oral lichen planus: A retrospective cohort study

“…In general, past studies have focused on dental metals and some smaller series have reported associations with fragrance, avoring, and preservative allergens. 10,11,13,[30][31][32] While metals and dental lling products can often be traced to a de ned source, the high burden of allergy to fragrance, avorings, and preservatives seen in our cohort is important and highlights the clinical di culty contact allergy may present in OLP since these allergens are often less apparent, more di cult to trace, and harder to avoid. The connection between these allergy ndings and clinical OLP phenotype or progression is unclear.…”

“…2,3,[6][7][8] Multiple case-series have emerged documenting cutaneous allergy in OLP. [9][10][11][12][13][14][15] One study has proposed that contact allergy, at least to metal, could initiate pathogenesis. 11 However, it is not generally known to what extent contact allergy drives pathogenesis or if avoidance improves disease.…”

“…[9][10][11][12][13][14][15] One study has proposed that contact allergy, at least to metal, could initiate pathogenesis. 11 However, it is not generally known to what extent contact allergy drives pathogenesis or if avoidance improves disease. The most common allergens reported are dental metals, but other allergens include dental resins, and fragrance mixes.…”

“…The most common allergens reported are dental metals, but other allergens include dental resins, and fragrance mixes. [9][10][11][12][13][14][15] The association between OLP and oral squamous cell carcinoma (oSCC) is well documented. 8,[16][17][18][19][20][21][22][23] Two large, multi-center retrospective cohort studies found oSCC to occur in 3.1% of OLP cases 20 years after diagnosis and 2.58% at 33 years after OLP diagnosis.…”

Metal Allergy: State-of-the-Art Mechanisms, Biomarkers, Hypersensitivity to Implants

“…The expansion of T cells at the lesion site collaborated with the formation of the oral lichen planus (OLP). T cells infiltration via TSLP-TSLP-receptor (TSLPR) signaling, and TNF-α production was higher in OLPs in metal-allergy patients compared to healthy controls [ 77 ].…”