Epigenetic regulation of sexually dimorphic immune responses in keratinocytes

项目摘要 在多种皮肤疾病中观察到炎症反应的失调，包括 自身免疫性疾病和感染。这些疾病的一个显著特征是与生殖系统有关的性二态性。 这些疾病在男女之间的发病率不同。了解潜在的 性别偏见炎症反应的机制可能指向以前未被认识的途径 这在调节免疫反应中至关重要，因此可能导致性特异性免疫反应的发展。 治疗方法。性激素和性染色体调控基因作用的研究现状 不足以解释男女之间的这些生物学差异。我们最近发现 男性和女性角质形成细胞之间的差异表观遗传修饰，为我们的研究奠定了基础。 角质形成细胞性二态表观遗传修饰影响免疫基因假说 转录和响应。该项目的目标是识别和靶向表观遗传修饰 驱动性二型免疫反应，允许未来开发精确治疗， 炎症性皮肤病在这个项目的成功完成后，我们将有特点， 女性和男性皮肤细胞之间的表观遗传差异，决定了这些性别偏见的贡献。 对免疫反应的表观遗传修饰，并评估它们是否可以作为治疗方法 免疫介导的皮肤病的未来治疗的目标。

PROJECT SUMMARY Dysregulation of inflammatory responses are observed in a variety of cutaneous diseases, including autoimmune diseases and infections. A striking feature of these conditions is sexual dimorphism relating to the differential incident rates of these diseases between women and men. Understanding the underlying mechanism for the sex-biased inflammatory responses can point towards previously unappreciated pathways that are critical in regulating immune responses, and therefor can lead to development of sex-specific therapeutic approaches. Current data on the effect of sex-hormones and sex-chromosome regulatory genes insufficiently explain these biologic differences between men and women. We have recently identified differential epigenetic modifications between male and female keratinocytes, setting the stage for our hypothesis that sexually dimorphic epigenetic modifications in keratinocytes affect immune gene transcription and responses. The objective of this project is to identify and target epigenetic modifications that drive sexually dimorphic immune responses, allowing future development of precision therapies for inflammatory skin disorders. Upon the successful completion of this project, we will have characterized epigenetic differences between skin cells in women and men, determined the contribution of these sex-biased epigenetic modifications to immunological responses, and assessed whether they could serve as therapeutic targets for future treatment of immune mediated skin disorders.