Regulatory T-cell dysfunction induces autoantibodies to bullous pemphigoid antigens in mice and human subjects

Ken Muramatsu, Hideyuki Ujiie, Ichiro Kobayashi, Wataru Nishie, Kentaro Izumi, Takamasa Ito, Norihiro Yoshimoto, Ken Natsuga, Hiroaki Iwata, Hiroshi Shimizu

doi:10.1016/j.jaci.2018.03.014

Regulatory T (Treg) cells play a crucial role in peripheral immune tolerance in multiple organs, including the skin. Thus far, the effect of peripheral immune tolerance failure on autoantibody-related autoimmune reactions to the skin is unclear.We sought to elucidate the target autoantigens in the skin under the condition of Treg cell dysfunction caused by forkhead box P3 (Foxp3) gene mutations in scurfy mice and patients with immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.Sera and skin from scurfy mice and sera from patients with IPEX syndrome were analyzed to detect target autoantigens by using immunofluorescence studies, ELISAs, and immunoblotting. The pathogenicity of scurfy IgG was examined by using a passive transfer experiment. CD4Scurfy mice spontaneously generated IgG autoantibodies to the dermal-epidermal junction, which had been class-switched from IgM within 12 days after birth. The target autoantigens were murine BP230 and type XVII collagen (COL17). The scurfy polyclonal autoantibodies did not induce skin fragility in neonatal mice. Autoantibody production was induced by CD4Dysregulation of Treg cells generates autoantibodies to COL17 and BP230 in vivo.

Regulatory T-cell dysfunction induces autoantibodies to bullous pemphigoid antigens in mice and human subjects

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Regulatory T-cell dysfunction induces autoantibodies to bullous pemphigoid antigens in mice and human subjects

書誌事項

この論文をさがす

説明

収録刊行物

被引用文献 (13)*注記

参考文献 (59)*注記

関連プロジェクト

キーワード

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