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分析斑秃作为毛囊周期自身免疫性疾病模型的动力学。

Analysing the dynamics of a model for alopecia areata as an autoimmune disorder of hair follicle cycling.

作者信息

Dobreva Atanaska, Paus Ralf, Cogan N G

机构信息

Department of Mathematics, Florida State University, Tallahassee, FL, USA.

Centre for Dermatology Research, University of Manchester, and NIHR Manchester Biomedical Research Centre, Manchester, UK.

出版信息

Math Med Biol. 2018 Sep 11;35(3):387-407. doi: 10.1093/imammb/dqx009.

Abstract

Alopecia areata (AA) is a CD8$^{+}$ T cell-dependent autoimmune disease that disrupts the constantly repeating cyclic transformations of hair follicles (HFs). Among the three main HF cycle stages-growth (anagen), regression (catagen) and relative quiescence (telogen)-only anagen HFs are attacked and thereby forced to prematurely enter into catagen, thus shortening active hair growth substantially. After having previously modelled the dynamics of immune system components critically involved in the disease development (Dobreva et al., 2015), we here present a mathematical model for AA which incorporates HF cycling and illustrates the anagen phase interruption in AA resulting from an inflammatory autoimmune response against HFs. The model couples a system describing the dynamics of autoreactive immune cells with equations modelling the hair cycle. We illustrate states of health, disease and treatment as well as transitions between them. In addition, we perform parameter sensitivity analysis to assess how different processes, such as proliferation, apoptosis and input from stem cells, impact anagen duration in healthy versus AA-affected HFs. The proposed model may help in evaluating the effectiveness of existing treatments and identifying new potential therapeutic targets.

摘要

斑秃(AA)是一种依赖CD8⁺ T细胞的自身免疫性疾病,它会破坏毛囊(HF)持续重复的周期性转变。在毛囊的三个主要周期阶段——生长(生长期)、退化(退行期)和相对静止期(休止期)中,只有生长期毛囊会受到攻击,从而被迫过早进入退行期,进而大幅缩短活跃毛发生长期。在之前对疾病发展过程中关键的免疫系统组成部分的动态变化进行建模之后(多布雷娃等人,2015年),我们在此提出一个针对斑秃的数学模型,该模型纳入了毛囊周期,并阐释了由于针对毛囊的炎症性自身免疫反应导致的斑秃生长期中断情况。该模型将一个描述自身反应性免疫细胞动态变化的系统与模拟毛发周期的方程相结合。我们阐释了健康、疾病和治疗状态以及它们之间的转变。此外,我们进行参数敏感性分析,以评估不同过程,如增殖、凋亡和干细胞输入,如何影响健康毛囊与受斑秃影响毛囊的生长期持续时间。所提出的模型可能有助于评估现有治疗方法的有效性并确定新潜在治疗靶点。

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