当前位置: X-MOL 学术J. Invest. Dermatol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Epidermal Damage Induces Th1 Polarization and Defines the Site of Inflammation in Murine Epidermolysis Bullosa Acquisita.
Journal of Investigative Dermatology ( IF 6.5 ) Pub Date : 2020-02-11 , DOI: 10.1016/j.jid.2020.01.022
Markus Niebuhr 1 , Katja Bieber 2 , David Banczyk 1 , Sebastian Maass 1 , Sebastian Klein 1 , Mareike Becker 3 , Ralf Ludwig 3 , Detlef Zillikens 4 , Jürgen Westermann 1 , Kathrin Kalies 1
Affiliation  

Epidermolysis bullosa acquisita is an autoimmune skin disease characterized by subepidermal blisters. The pathogenesis is mediated by deposits of autoantibodies directed against type VII collagen in the skin, but the sequence of events regulating the localization of skin blisters is not fully understood. In this study, using the immunization-induced mouse model of epidermolysis bullosa acquisita, we demonstrate that epidermal disruption induces not only an infiltration of CD4+ T cells but also a T helper type 1 phenotype as it has been described for delayed-type hypersensitivity reactions. This T helper type 1 reaction was not found when different antigens were applied. Deep T-cell receptor β profiling revealed shifts in the V/J gene usage only in epidermolysis bullosa acquisita, suggesting an infiltration of autoantigen-specific T cells. To target these autoantigen-specific T cells, we established an approach with which skin inflammation could be prevented without impairing the functionality of autoantibodies. We conclude that T-cell involvement in skin blistering diseases such as epidermolysis bullosa acquisita relates not only to T-cell help for B cells that produce pathogenic autoantibodies but also to autoreactive T helper type 1 effector cells that migrate into injured skin sites, exacerbate inflammation through production of inflammatory cytokines such as IFNγ, and prevent wound healing.



中文翻译:

表皮损伤诱导Th1极化并确定小鼠表皮松解大疱性炎症中的炎症部位。

大疱表皮松解症是一种以表皮下水泡为特征的自身免疫性皮肤病。发病机理是由针对皮肤中的VII型胶原的自身抗体沉积介导的,但调节皮肤水泡定位的事件顺序尚不完全清楚。在这项研究中,使用免疫诱导的大疱性表皮松解小鼠模型,我们证明表皮破坏不仅诱导CD4 +的浸润T细胞,但也有T辅助1型表型,如针对迟发型超敏反应所描述的。当应用不同的抗原时,未发现这种1型T辅助反应。深T细胞受体β谱分析仅在表皮松解性大疱性水肿中揭示了V / J基因使用的变化,表明自身抗原特异性T细胞的浸润。为了靶向这些自身抗原特异性T细胞,我们建立了一种可以在不损害自身抗体功能的情况下预防皮肤炎症的方法。我们得出的结论是,T细胞参与皮肤疱疹性疾病(例如大疱性表皮松解症)不仅涉及产生致病性自身抗体的B细胞对T细胞的帮助,而且还涉及迁移到受损皮肤部位的自身反应性T辅助1型效应细胞,

更新日期:2020-02-11
down
wechat
bug