Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous Kitwsh/wsh mutation

• Published in: Modern rheumatology 2018-03, Vol.28 (2), p.319-326
• Main Authors: Inaba, Yutaka, Kanazawa, Nobuo, Yoshimasu, Takashi, Shimokawa, Toshio, Nosaka, Mizuho, Kondo, Toshikazu, Furukawa, Fukumi
• Format: Article
• Language: English
• Subjects: c-kit; mast cell; MRL/lpr mice; systemic lupus erythematosus
• ISSN: 1439-7595; 1439-7609
• DOI: 10.1080/14397595.2017.1341591

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 wsh/wsh mice and the heterozygous F1 mice were 10 times backcrossed with the parental MRL/lpr to generate MRL/lpr-Kit wsh/wsh mice. MC-deficient MRL/lpr-Kit wsh/wsh mice were compared with MRL/lpr-Kit +/+ and MRL/lpr-Kit wsh/+ mice with intact MCs. Results: MRL/lpr-Kit wsh/wsh mice developed skin lesions without infiltrating MCs. As similar skin lesions on MRL/lpr-Kit +/+ mice and MRL/lpr-Kit wsh/+ 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.