Epigenetic regulation of sexually dimorphic immune responses in keratinocytes

项目总结 炎症反应的失调在各种皮肤病中观察到，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 这些疾病在女性和男性之间的发病率不同。了解潜在的 性别偏向炎症反应的机制可能指向以前未被认识到的途径 它们在调节免疫反应中起关键作用，因此可以导致性别特异性的发展。 治疗方法。性激素和性染色体调控基因作用的最新数据 不能充分解释男性和女性之间的这些生物差异。我们最近确认了 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 角质形成细胞性二态表观遗传修饰影响免疫基因的假说 转录和反应。这个项目的目标是确定和瞄准表观遗传修饰 驱动性二型性免疫反应，使未来能够开发精确的治疗方法 炎症性皮肤病。在这个项目成功完成后，我们将具有 女性和男性皮肤细胞的表观遗传学差异，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用作治疗 未来免疫介导性皮肤病治疗的目标。

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.