Warren Bryce D, Kinsey William K, McGinnis Lynda K, Christenson Lane K, Jasti Susmita, Stevens Anne M, Petroff Brian K, Petroff Margaret G
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, USA.
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
Cell Mol Immunol. 2014 Nov;11(6):510-21. doi: 10.1038/cmi.2014.97. Epub 2014 Oct 20.
The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models.
卵巢并非免疫特惠器官，但针对卵巢特异性抗原的耐受机制失灵会对女性生育能力造成灾难性后果，且在自身免疫性疾病的小鼠模型中也会出现这种情况。孤立性卵巢自身免疫性疾病在女性中较为罕见，这可能是由于该疾病的严重性以及无法将导致卵巢疾病的遗传信息代代相传。尽管如此，自身免疫性卵巢炎常与其他自身免疫性疾病相关，尤其是自身免疫性肾上腺疾病，对社会和个人健康都造成了损害。对小鼠的研究揭示了至少两种保护卵巢免受自身免疫攻击的机制。这些机制包括胸腺来源的调节性T细胞对自身反应性T细胞的控制，以及自身免疫调节因子（AIRE）的作用，AIRE是一种转录调节因子，在T细胞发育过程中诱导髓质胸腺上皮细胞表达组织限制性抗原。尽管后一种机制尚未完全明确，但已充分证实，任何一种机制失灵都会导致自身免疫介导的卵巢卵泡靶向性破坏和耗竭。在本综述中，我们将探讨女性自身免疫介导的卵巢性不孕的临床特征和后果，以及动物模型所揭示的可能的疾病机制。
