Delineating Immune-Mediated Mechanisms Underlying Hair Follicle Destruction in the Mouse Mutant Defolliculated
Delineating Immune-Mediated Mechanisms Underlying Hair Follicle Destruction in the Mouse Mutant Defolliculated
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DOI：
10.1038/jid.2010.379
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发表时间：
2011-03-01
影响因子：
6.5
通讯作者：
Porter, Rebecca M.
中科院分区：
文献类型：
--
作者：
Ruge, Fiona;Glavini, Aikaterini;Porter, Rebecca M.
去毛囊(Gsdma3(DFL)/+)小鼠的脱毛表型包括毛发周期异常、皮脂腺分化改变、皮脂生成减少、慢性炎症，最终导致毛囊脱落。这些小鼠的脱发与原发性瘢痕性脱发相似，在这些脱发中，毛囊干细胞的免疫靶向被认为是导致永久毛囊破坏的关键因素。在这项研究中，我们研究了GsdmA3(DFL)/+小鼠脱发的机制。干细胞标志物在毛发周期中的异常表达模式，以及导致毛囊和表皮异位色素沉积的黑素细胞的异常行为，表明干细胞生态位没有维持。通过将小鼠与RAG1-/-小鼠杂交，排除了自身免疫机制。然而，大量巨噬细胞和ICAM-1的表达增加仍然存在，可能直接或间接参与了脱发。逆转录-聚合酶链式反应(RT-PCR)和皮脂腺分化标记物的免疫组织化学检测显示，脱发患者体内过氧化体增殖物激活受体-γ(PPAR-Gamma)表达降低，这是皮脂产生减少的一个潜在原因，也可能与先天免疫系统有关。由于PPARγ表达降低最近被认为是扁平苔藓的原因之一，这些小鼠可能有助于测试治疗方法。
Defolliculated (Gsdma3(Dfl)/+) mice have a hair loss phenotype that involves an aberrant hair cycle, altered sebaceous gland differentiation with reduced sebum production, chronic inflammation, and ultimately the loss of the hair follicle. Hair loss in these mice is similar to that seen in primary cicatricial, or scarring alopecias in which immune targeting of hair follicle stem cells has been proposed as a key factor resulting in permanent hair follicle destruction. In this study we examine the mechanism of hair loss in GsdmA3(Dfl)/+ mice. Aberrant expression patterns of stem cell markers during the hair cycle, in addition to aberrant behavior of the melanocytes leading to ectopic pigmentation of the hair follicle and epidermis, indicated the stem cell niche was not maintained. An autoimmune mechanism was excluded by crossing the mice with rag1-/- mice. However, large numbers of macrophages and increased expression of ICAM-1 were still present and may be involved either directly or indirectly in the hair loss. Reverse transcriptase-PCR (RT-PCR) and immunohistochemistry of sebaceous gland differentiation markers revealed reduced peroxisome proliferator-activated receptor-gamma (PPAR gamma), a potential cause of reduced sebum production, as well as the potential involvement of the innate immune system in the hair loss. As reduced PPAR gamma expression has recently been implicated as a cause for lichen planopilaris, these mice may be useful for testing therapies.