Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous Kitwsh/wsh 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 wsh/wsh mice and the heterozygous F1 mice were 10 times backcrossed with the parental MRL/lpr to generate MRL/lpr-K...

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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
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Language:English
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c-kit
mast cell
MRL/lpr mice
systemic lupus erythematosus
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container_issue 2
container_start_page 319
container_title Modern rheumatology
container_volume 28
creator Inaba, Yutaka
Kanazawa, Nobuo
Yoshimasu, Takashi
Shimokawa, Toshio
Nosaka, Mizuho
Kondo, Toshikazu
Furukawa, Fukumi
description 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.
doi_str_mv 10.1080/14397595.2017.1341591
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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.</description><identifier>ISSN: 1439-7595</identifier><identifier>EISSN: 1439-7609</identifier><identifier>DOI: 10.1080/14397595.2017.1341591</identifier><language>eng</language><publisher>Taylor &amp; Francis</publisher><subject>c-kit ; mast cell ; MRL/lpr mice ; systemic lupus erythematosus</subject><ispartof>Modern rheumatology, 2018-03, Vol.28 (2), p.319-326</ispartof><rights>2017 Japan College of Rheumatology 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Inaba, Yutaka</creatorcontrib><creatorcontrib>Kanazawa, Nobuo</creatorcontrib><creatorcontrib>Yoshimasu, Takashi</creatorcontrib><creatorcontrib>Shimokawa, Toshio</creatorcontrib><creatorcontrib>Nosaka, Mizuho</creatorcontrib><creatorcontrib>Kondo, Toshikazu</creatorcontrib><creatorcontrib>Furukawa, Fukumi</creatorcontrib><title>Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous Kitwsh/wsh mutation</title><title>Modern rheumatology</title><description>Objective: To clarify the roles of mast cells (MCs) on the pathogenesis of lupus erythematosus (LE)-like skin lesions on MRL/lpr mice. 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Conclusions: These results demonstrated that MCs are infiltrated to suppress the progression of LE-like skin lesions in MRL/lpr mice.</abstract><pub>Taylor &amp; Francis</pub><doi>10.1080/14397595.2017.1341591</doi><tpages>8</tpages></addata></record>
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subjects c-kit
mast cell
MRL/lpr mice
systemic lupus erythematosus
title Severer lupus erythematosus-like skin lesions in MRL/lpr mice with homozygous Kitwsh/wsh mutation
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