Apoptotic cell responses in the splenic marginal zone: a paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity.
Apoptotic cell responses in the splenic marginal zone: a paradigm for immunologic reactions to apoptotic antigens with implications for autoimmunity.
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DOI：
10.1111/imr.12382
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发表时间：
2016-01
影响因子：
8.7
通讯作者：
Karlsson MC
中科院分区：
文献类型：
--
作者：
McGaha TL;Karlsson MC
凋亡细胞驱动先天性调节反应，导致耐受性免疫。这是细胞生理学的一个关键方面，因为凋亡细胞在凋亡泡的表面上暴露潜在危险的核抗原，并且它们的识别、吞噬作用，边缘区是脾的一个特殊环境，是从血液循环到外周淋巴系统的过渡部位，结构.边缘区在捕获颗粒物和启动针对全身性微生物病原体的先天反应中起关键作用。然而，近年来已经清楚的是，边缘区对于启动对凋亡细胞的免疫耐受也很重要，驱动涉及多个吞噬细胞和淋巴细胞亚群的协调反应。最近的报告链接缺陷脾巨噬细胞的功能，以类似于边缘区巨噬细胞在狼疮倾向的小鼠的方式SLE提供了一个动力，以更好地了解在边缘区的凋亡细胞反应的机制基础，其一般适用于凋亡细胞驱动的耐受性在其他组织部位。在这篇综述中，我们讨论了免疫反应的凋亡细胞在脾脏一般和边缘区，特别是这些反应的关系，自身免疫性疾病，并比较人类的凋亡细胞免疫。
Apoptotic cells drive innate regulatory responses that result in tolerogenic immunity. This is a critical aspect of cell physiology as apoptotic cells expose potentially dangerous nuclear antigens on the surface in apoptotic blebs, and failure in their recognition, phagocytosis, or destruction can cause dramatic autoimmunity in experimental models and is linked to development and progression of systemic pathology in man. The marginal zone is a specialized splenic environment that serves as a transitional site from circulation to peripheral lymphoid structures. The marginal zone serves a key role in trapping of particulates and initiation of innate responses against systemic microbial pathogens. However in recent years it has become clear the marginal zone is also important for initiation of immune tolerance to apoptotic cells, driving a coordinated response involving multiple phagocyte and lymphocyte subsets. Recent reports linking defects in splenic macrophage function to SLE in a manner analogous to marginal zone macrophages in lupus-prone mice provides an impetus to better understand the mechanistic basis of the apoptotic cell response in the marginal zone and its general applicability to apoptotic cell-driven tolerance at other tissue sites. In this review we discuss immune responses to apoptotic cells in the spleen in general and the marginal zone in particular, the relationship of these responses to autoimmune disease, and comparisons to apoptotic cell immunity in humans.