Targeting DAMPs with nucleic acid scavengers to treat lupus.
Targeting DAMPs with nucleic acid scavengers to treat lupus.
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用核酸清除剂靶向DAMP以治疗狼疮。
DOI：
10.1016/j.trsl.2022.02.007
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发表时间：
2022-07
影响因子：
7.8
通讯作者：
SULLENGER, B. R. U. C. E. A.
中科院分区：
文献类型：
--
作者：
OLSON, L. Y. R. A. B.;HUNTER, N. I. C. O. L. E. I.;REMPEL, R. A. C. H. E. L. E.;SULLENGER, B. R. U. C. E. A.
系统性红斑狼疮（SLE）是一种慢性进行性自身免疫性疾病，临床表现为一系列不同的症状，包括疲劳、皮疹、关节痛和肾损害。肺、心脏、胃肠系统和大脑也会受到影响，患有狼疮的人患动脉粥样硬化、血栓形成、甲状腺疾病和其他与慢性炎症相关的疾病的风险更高。自身免疫性疾病以错误的免疫反应为标志，其中免疫反应的目标是“自身”抗原或自身抗原，由抗原特异性B细胞或T细胞的发育驱动，这些细胞克服了B细胞和T细胞发育中建立的正常的自我耐受系统。SLE的特点是产生针对核酸及其结合蛋白的自身抗体，包括抗双链DNA、抗smith（一种RNA结合蛋白）等。这些抗体结合它们的核源抗原形成免疫复合物，通过直接沉积在组织中和激活先天免疫细胞造成损伤和疤痕。在超过50%的SLE患者中，肾脏中的免疫复合物聚集导致肾内炎症和损伤，并导致狼疮肾炎，肾小球的进行性破坏是狼疮相关死亡的最常见原因之一。为了对抗这种病理，越来越多的注意力转向开发方法来减少这种自身抗体的发展和持续产生。特别是，导致这种自身免疫反应长期持续激活的分子和细胞事件已成为限制狼疮患者肾脏和其他病理的新治疗策略的焦点。本综述的重点是考虑先天免疫系统如何参与狼疮肾炎的发生和进展，以及如何通过中和这种反应的激活因子来抑制先天免疫激活的新方法，称为损伤相关分子模式（DAMPs），可能代表治疗这种疾病和其他自身免疫性疾病的有希望的方法。
Systemic lupus erythematosus (SLE) is a chronic and often progressive autoimmune disorder marked clinically by a variable constellation of symptoms including fatigue, rash, joint pains, and kidney damage. The lungs, heart, gastrointestinal system, and brain can also be impacted, and individuals with lupus are at higher risk for atherosclerosis, thrombosis, thyroid disease, and other disorders associated with chronic inflammation. Autoimmune diseases are marked by erroneous immune responses in which the target of the immune response is a “self”-antigen, or autoantigen, driven by the development of antigen-specific B or T cells that have overcome the normal systems of self-tolerance built into the development of B and T cells. SLE is specifically characterized by the production of autoantibodies against nucleic acids and their binding proteins, including anti-double stranded DNA, anti-Smith (an RNA binding protein), and many others. These antibodies bind their nuclear-derived antigens to form immune complexes that cause injury and scarring through direct deposition in tissues and activation of innate immune cells. In over 50% of SLE patients, immune complex aggregation in the kidneys drives intrarenal inflammation and injury and leads to lupus nephritis, a progressive destruction of the glomeruli that is one of the most common causes of lupus-related death. To counter this pathology increasing attention has turned to developing approaches to reduce the development and continued generation of such autoantibodies. In particular, the molecular and cellular events that lead to long term, continuous activation of such autoimmune responses have become the focus of new therapeutic strategies to limit renal and other pathologies in lupus patients. The focus of this review is to consider how the innate immune system is involved in the development and progression of lupus nephritis and how a novel approach to inhibit innate immune activation by neutralizing the activators of this response, called Damage Associated Molecular Patterns (DAMPs), may represent a promising approach to treat this and other autoimmune disorders.
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