Susceptibility of T cell receptor-αchain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus

Abstract

SUMMARYThe anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-a -/-mice and B6 TCR-d -/-mice treated with FU and/ or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-a -/-mice with low FU (0·2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2·0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-d -/-mice at a very low incidence. Specifically, the skin lesions of TCR-a -/-mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE.

Clonal expansion of Epstein–Barr virus (EBV)-infected γδ T cells in patients with chronic active EBV disease and hydroa vacciniforme-like eruptions

“…Studies in a murine model for drug-induced cutaneous lupus erythematosus demonstrated that ultraviolet might enhance the function of skin  T cells that were involved in skin lesions [27]. Therefore, EBV-infected  T cells may play an important role in the skin lesions of HV.…”

Anti-SSA/Ro Antibody as a Risk Factor for Fluorouracil-Induced Drug Eruptions Showing Acral Erythema and Discoid-Lupus-Erythematosus-Like Lesions

“…It is therefore plausible to speculate that these chemotherapeutic agents translocate SSA/Ro antigen to the surface of cultured keratinocytes in a manner similar to UVB light. Interestingly, it has been shown that a combined treatment of FU and UVB strongly induces cutaneous-LE-like eruptions in mice [11, 12]. The tendency that DLE-like eruptions are located in sun-exposed areas of the skin further suggests that ultraviolet rays and these anticancer agents cooperate in inducing these skin symptoms.…”

Occurrence of subacute cutaneous lupus erythematosus after treatment with fluorouracil and capecitabine

“…1,2 The exact pathomechanism eliciting SCLE by 5-FU or capecitabine is not yet fully known. Yoshimasu et al 14 showed that T-cell receptor-alpha chain knockout mice developed cutaneous lupus erythematosus when treated with 5-FU and ultraviolet-B light. Whereas 5-FU causes damage to the basal layers of the epidermis, ultraviolet-B light leads to the translocation of Ro antigens to the surface of keratinocytes.…”