Freyschmidt-Paul Pia, Happle Rudolf, Hoffman Rolf
Universitäts-Hautklinik der Philipps-Universität Marburg.
J Dtsch Dermatol Ges. 2004 Apr;2(4):260-73. doi: 10.1046/j.1610-0387.2003.03553.x-i1.
Alopecia areata is a common disease, but for ethical reasons it seems difficult to perform large-scale studies to elucidate the pathogenesis and to develop new therapeutic approaches in man. It is therefore helpful to develop appropriate animal models. The Dundee experimental bald rat (DEBR) and the C3H/HeJ mouse are well-established animal models for alopecia areata and can be used for the study of genetic aspects, pathogenesis and therapy of the disease. In C3H/HeJ mice alopecia areata can be experimentally induced by grafting lesional skin from an affected mouse to a histocompatible recipient which offers the possibility to study the influence of various factors on the development of the disease. Studies on the C3H/HeJ mouse and the DEBR have corroborated the concept that alopecia areata is a T-cell mediated autoimmune disease and various steps and aspects of the pathogenesis have been elucidated. Based on this knowledge new therapeutic options may be developed such as inhibition of lymphocyte-homing by an anti-CD44v10 antibody, or inhibition of costimulation by monoclonal antibodies. Therapeutic studies in the C3H/HeJ mouse and the DEBR suggest that alopecia areata can be treated by topical tacrolimus but treatment in humans may only be successful after development of an improved vehicle that facilitates penetration of tacrolimus down to the hair bulb. Current investigations in mice are designed to elucidate the mechanisms how contact sensitizers act in the treatment of alopecia areata, and this will hopefully lead to the development of more specific approaches based on the beneficial effect of contact sensitizers.
斑秃是一种常见疾病,但出于伦理原因,开展大规模研究以阐明其发病机制并开发新的治疗方法似乎存在困难。因此,开发合适的动物模型会有所帮助。邓迪实验性秃头大鼠(DEBR)和C3H/HeJ小鼠是成熟的斑秃动物模型,可用于研究该疾病的遗传因素、发病机制和治疗方法。在C3H/HeJ小鼠中,通过将患病小鼠的病变皮肤移植到组织相容性受体上可实验性诱导斑秃,这为研究各种因素对疾病发展的影响提供了可能性。对C3H/HeJ小鼠和DEBR的研究证实了斑秃是一种T细胞介导的自身免疫性疾病的概念,并阐明了发病机制的各个步骤和方面。基于这些知识,可能会开发出新的治疗选择,例如用抗CD44v10抗体抑制淋巴细胞归巢,或用单克隆抗体抑制共刺激。在C3H/HeJ小鼠和DEBR上进行的治疗研究表明,局部使用他克莫司可治疗斑秃,但在开发出能促进他克莫司渗透至毛囊球部的改良载体后,人类治疗才可能取得成功。目前在小鼠身上进行的研究旨在阐明接触致敏剂治疗斑秃的作用机制,有望基于接触致敏剂的有益效果开发出更具特异性的方法。