CD11b Activity Modulates Pathogenesis of Lupus Nephritis.
CD11b Activity Modulates Pathogenesis of Lupus Nephritis.
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DOI：
10.3389/fmed.2018.00052
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发表时间：
2018
影响因子：
3.9
通讯作者：
Gupta V
中科院分区：
文献类型：
--
作者：
Khan SQ;Khan I;Gupta V
狼疮性肾炎（LN）是系统性红斑狼疮（SLE）的常见并发症，病因不明，治疗方法有限。免疫细胞浸润到肾脏，LN的标志，触发组织损伤和蛋白尿。CD 11b是整合素受体CD 11b/CD 18（也称为αMβ2、Mac-1和CR 3）的α链，在先天性免疫细胞（包括巨噬细胞和中性粒细胞）表面高度表达。编码CD 11b的人类ITGAM基因的遗传变异与SLE、LN和其他SLE并发症的易感性密切相关。CD 11b调节先天免疫细胞中的几种关键生物学功能，包括细胞粘附、迁移和吞噬作用。CD 11b还调节这些细胞中的其他信号传导途径，例如Toll样受体信号传导途径，其介导I型干扰素的产生，I型干扰素是SLE和LN患者中的关键促炎细胞因子和循环生物标志物。然而，ITGAM基因的变异如何导致疾病的发病机制尚未完全确定。在这里，我们提供了一个概述CD 11b调制机制和功能的遗传变异，可以驱动疾病的发病机制的后果。我们还提出了最近的见解，从药理学激活后的CD 11b的研究。这些研究为LN、SLE和其他自身免疫性疾病的治疗提供了新的机制。
Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) with unclear etiology and limited treatment options. Immune cell infiltration into the kidneys, a hallmark of LN, triggers tissue damage and proteinuria. CD11b, the α-chain of integrin receptor CD11b/CD18 (also known as αMβ2, Mac-1, and CR3), is highly expressed on the surface of innate immune cells, including macrophages and neutrophils. Genetic variants in the human ITGAM gene, which encodes for CD11b, are strongly associated with susceptibility to SLE, LN, and other complications of SLE. CD11b modulates several key biological functions in innate immune cells, including cell adhesion, migration, and phagocytosis. CD11b also modulates other signaling pathways in these cells, such as the Toll-like receptor signaling pathways, that mediate generation of type I interferons, a key proinflammatory cytokine and circulating biomarker in SLE and LN patients. However, how variants in ITGAM gene contribute to disease pathogenesis has not been completely established. Here, we provide an overview of CD11b modulated mechanisms and the functional consequences of the genetic variants that can drive disease pathogenesis. We also present recent insights from studies after pharmacological activation of CD11b. These studies offer novel mechanisms for development of therapeutics for LN, SLE and other autoimmune diseases.
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