Sánchez-Pernaute Olga, Ospelt Caroline, Neidhart Michel, Gay Steffen
Fundación Jiménez Díaz, Madrid, Spain.
J Autoimmun. 2008 Feb-Mar;30(1-2):12-20. doi: 10.1016/j.jaut.2007.11.006. Epub 2007 Dec 26.
The innate immune response needs to be tightly regulated to balance elimination of microorganisms with the magnitude of inflammation. The rupture of this balance is crucial for the outcome of diseases such as rheumatoid arthritis (RA) in which an overflowed proinflammatory response is associated with self-damage. Epigenetics alludes to systems controlling gene expression and silencing independent of the germline, but stable enough to be inherited by daughter cells upon mitosis. We will show in this review how pathological processes in RA can be shaped by epigenetics, which may in turn explain differences in phenotypes between subgroups of patients and also between subsets of fibroblasts within the joint. On the whole, the concourse of epigenetic mechanisms can precipitate the aggressive behaviour of cells and the rupture of peripheral tolerance. Targeting these emerging regulatory pathways is a promising approach for RA therapeutics.
先天性免疫反应需要严格调控，以平衡微生物的清除与炎症的程度。这种平衡的打破对于类风湿性关节炎（RA）等疾病的结局至关重要，在RA中，过度的促炎反应与自身损伤相关。表观遗传学是指控制基因表达和沉默的系统，该系统独立于种系，但足够稳定，能够在有丝分裂时由子细胞继承。在本综述中，我们将展示RA中的病理过程如何由表观遗传学塑造，这反过来可能解释患者亚组之间以及关节内成纤维细胞亚群之间表型的差异。总体而言，表观遗传机制的共同作用可促使细胞的侵袭性行为和外周耐受性的打破。针对这些新出现的调节途径是RA治疗的一种有前景的方法。
