Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous Kit mutation.

OBJECTIVE

To clarify the roles of mast cells (MCs) on the pathogenesis of lupus erythematosus (LE)-like skin lesions on MRL/lpr mice.

METHODS

MRL/lpr mice were mated with C57BL/6-Kit mice and the heterozygous F1 mice were 10 times backcrossed with the parental MRL/lpr to generate MRL/lpr-Kit mice. MC-deficient MRL/lpr-Kit mice were compared with MRL/lpr-Kit and MRL/lpr-Kit mice with intact MCs.

RESULTS

MRL/lpr-Kit mice developed skin lesions without infiltrating MCs. As similar skin lesions on MRL/lpr-Kit mice and MRL/lpr-Kit mice contain comparable number of MCs, these mice were collectively analyzed as MRL/lpr mice with MCs. Compared with MRL/lpr mice with MCs, skin lesions developed earlier and showed consistently higher severity, with significantly higher mRNA expressions of many inflammatory cytokines in the dorsal skin on MRL/lpr mice without MCs. Furthermore, survival rate was significantly lower in MRL/lpr mice without MCs. The number of infiltrating MCs significantly increased in association with the severity of skin lesions in MRL/lpr mice with MCs.

CONCLUSIONS

These results demonstrated that MCs are infiltrated to suppress the progression of LE-like skin lesions in MRL/lpr mice.