Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous <i>Kit<sup>wsh/wsh</sup></i> mutation

<p><b>Objective:</b> To clarify the roles of mast cells (MCs) on the pathogenesis of lupus erythematosus (LE)-like skin lesions on MRL/lpr mice.</p> <p><b>Methods:</b> MRL/lpr mice were mated with C57BL/6-<i>Kit<sup>wsh/wsh</sup> </i>mice and the heterozygous F1 mice were 10 times backcrossed with the parental MRL/lpr to generate MRL/lpr-<i>Kit<sup>wsh/wsh</sup> </i>mice. MC-deficient MRL/lpr-<i>Kit<sup>wsh/wsh</sup></i> mice were compared with MRL/lpr-<i>Kit<sup>+/+</sup></i> and MRL/lpr-<i>Kit<sup>wsh/+</sup></i> mice with intact MCs.</p> <p><b>Results:</b> MRL/lpr-<i>Kit<sup>wsh/wsh</sup></i> mice developed skin lesions without infiltrating MCs. As similar skin lesions on MRL/lpr-<i>Kit<sup>+/+</sup></i> mice and MRL/lpr-<i>Kit<sup>wsh/+</sup></i> 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.</p> <p><b>Conclusions:</b> These results demonstrated that MCs are infiltrated to suppress the progression of LE-like skin lesions in MRL/lpr mice.</p>