狼疮性肾炎(LN)是系统性红斑狼疮(SLE)的严重和常见表现,经常被确定为预后不良。巨噬细胞在其发病机制中起重要作用。不同的巨噬细胞亚型对狼疮受累的肾脏有不同的影响。基于它们的起源,巨噬细胞可分为单核细胞衍生的巨噬细胞(MoMacs)和组织驻留的巨噬细胞(TrMacs)。在肾炎期间,TrMacs发展出一种混合的促炎和抗炎功能表型,因为它们在受细胞因子刺激时不分泌精氨酸酶或一氧化氮(NO)。这些混合表型巨噬细胞的浸润与免疫复合物和暴露于循环炎症介质引起的持续损伤有关,这是无法解决炎症的迹象。另一方面,MoMac在细胞因子刺激下分化成M1或M2细胞。M1巨噬细胞是促炎的,分泌促炎细胞因子,而M2主要表型本质上是抗炎和促进组织修复。相反,响应于细胞因子刺激,MoMac经历分化成M1或M2细胞。M1巨噬细胞被认为是促炎细胞和分泌促炎介质,而M2主要表型主要是抗炎和促进组织修复。此外,基于细胞因子的表达,M2巨噬细胞可进一步分为M2a、M2b,和M2c表型。M2a和M2c具有抗炎作用,参与组织修复,而M2b细胞具有免疫调节和促炎特性。Further,记忆巨噬细胞也在LN的发展中起作用。研究表明,巨噬细胞的极化受多种代谢途径控制,比如糖酵解,磷酸戊糖途径,脂肪酸氧化,鞘脂代谢,三羧酸循环,和精氨酸代谢。这些代谢途径的变化可以受到鱼油等物质的调节,多烯磷脂酰胆碱,牛磺酸,富马酸,二甲双胍,和沙丁胺醇,抑制巨噬细胞的M1极化,促进M2极化,从而减轻LN。
Lupus nephritis (LN) is a severe and common manifestation of systemic lupus erythematosus (SLE) that is frequently identified with a poor prognosis. Macrophages play an important role in its pathogenesis. Different macrophage subtypes have different effects on lupus-affected kidneys. Based on their origin, macrophages can be divided into monocyte-derived macrophages (MoMacs) and tissue-resident macrophages (TrMacs). During nephritis, TrMacs develop a hybrid pro-inflammatory and anti-inflammatory functional phenotype, as they do not secrete arginase or nitric oxide (NO) when stimulated by cytokines. The infiltration of these mixed-phenotype macrophages is related to the continuous damage caused by immune complexes and exposure to circulating inflammatory mediators, which is an indication of the failure to resolve inflammation. On the other hand, MoMacs differentiate into M1 or M2 cells under cytokine stimulation. M1 macrophages are pro-inflammatory and secrete pro-inflammatory cytokines, while the M2 main phenotype is essentially anti-inflammatory and promotes tissue repair. Conversely, MoMacs undergo differentiation into M1 or M2 cells in response to cytokine stimulation. M1 macrophages are considered pro-inflammatory cells and secrete pro-inflammatory mediators, whereas the M2 main phenotype is primarily anti-inflammatory and promotes tissue repair. Moreover, based on cytokine expression, M2 macrophages can be further divided into M2a, M2b, and M2c phenotypes. M2a and M2c have anti-inflammatory effects and participate in tissue repair, while M2b cells have immunoregulatory and pro-inflammatory properties. Further, memory macrophages also have a role in the advancement of LN. Studies have demonstrated that the
polarization of macrophages is controlled by multiple metabolic pathways, such as glycolysis, the pentose phosphate pathway, fatty acid oxidation, sphingolipid metabolism, the tricarboxylic acid cycle, and arginine metabolism. The changes in these metabolic pathways can be regulated by substances such as fish oil, polyenylphosphatidylcholine, taurine, fumaric acid, metformin, and salbutamol, which inhibit M1
polarization of macrophages and promote M2
polarization, thereby alleviating LN.