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Reduced TLR3 and TLR9 Expression in Epidermodysplasia Verruciformis: Evidence From a Comparative Skin Study
Luis Alberto Ribeiro Fróes1, Cibele Conceição Dos Apóstolos Pereira2, Lana Luiza da Cruz Silva2
1Department of Pathology, University of São Paulo Medical School, São Paulo, Brazil.
Journal of Medical Virology
|November 10, 2025
Summary
Epidermodysplasia verruciformis (EV) patients show reduced expression of Toll-like receptors (TLRs) 3 and 9. This suggests innate immune deficiencies may contribute to β-human papillomavirus persistence in EV.
Area of Science:
- Dermatology
- Immunology
- Genetics
Background:
- Epidermodysplasia verruciformis (EV) is a rare genodermatosis linked to β-human papillomavirus (β-HPV) persistence.
- Genetic mutations (TMC6, TMC8, CIB1) are known drivers, but innate immune roles are unclear.
Purpose of the Study:
- To quantify Toll-like receptor (TLR) expression in EV patients.
- To investigate the role of innate immunity in β-HPV persistence in EV.
Main Methods:
- Immunohistochemical analysis of TLR3, TLR4, TLR5, and TLR9 expression.
- Digital morphometry of epidermal keratinocytes in 135 skin specimens (EV and non-EV controls).
Main Results:
- EV patients had significantly lower TLR3 and TLR9 expression in normal skin and warts.
- TLR4 and TLR5 levels were similar between EV patients and controls.
- Normal skin warts in non-EV individuals showed increased TLR3, an absent response in EV patients.
Conclusions:
- EV patients exhibit an impaired epithelial innate-sensing phenotype.
- Innate immune deficiencies may exacerbate keratinocyte abnormalities and immune dysfunction in EV.
- Findings support exploring TLR-based therapies for Epidermodysplasia verruciformis.
