This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also highlight future treatment opportunities and therapeutics that will safely and efficiently restore hair growth and maintain patients in remission.

AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions. Interestingly, most of these diseases have been linked to compromised central and peripheral tolerance, and increased intestinal inflammation with enhanced gut permeability. Break of tolerance and priming of the autoreactive T-cells to attack antigenic epitopes in the hair follicle most likely requires several steps which include escape from negative selection and compromised peripheral tolerance. Local skin-related changes are also of importance due to the patchy manifestation of the skin areas with loss of hair, particularly in the early disease. Here, we discuss the defective mechanisms of tolerance, both central and peripheral, and hypothesize that the disease is driven by areas of tolerance break, and that these could be targeted for successful therapeutic interventions.

这篇综述旨在解决免疫耐受性受损的机制，从而促进脱发症（AA）的发展和维持。我们的目标还在于突出未来的治疗机会和疗法，这些疗法和疗法将安全有效地恢复头发生长并保持患者的缓解。

AA是一种推定的自身免疫性疾病，与多种其他自身免疫性疾病同时发生并在基因上集群。在这篇综述中，我们关注在这些其他自身免疫性疾病中从机理研究和药物开发中获得的经验。有趣的是，大多数这些疾病都与中枢和外周耐受性降低，肠道炎症增加和肠道通透性增加有关。破坏耐受性并激发自身反应性T细胞攻击毛囊中的抗原表位，最有可能需要几个步骤，其中包括逃避阴性选择和受损的外周耐受性。由于皮肤区域的斑块表现以及脱发，特别是在早期疾病中，局部皮肤相关的变化也很重要。这里，