Macrophages: The Good, the Bad, and the Gluttony.
Macrophages: The Good, the Bad, and the Gluttony.
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巨噬细胞：好、坏和暴食。
DOI：
10.3389/fimmu.2021.708186
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发表时间：
2021
影响因子：
7.3
通讯作者：
Johnson JR
中科院分区：
文献类型：
--
作者：
Ross EA;Devitt A;Johnson JR
巨噬细胞是动态细胞，在无菌性炎症的诱导和消退中发挥关键作用。在这篇综述中，我们将编译和解释最近的研究结果，巨噬细胞的可塑性，以及这些细胞如何有助于非感染性炎症性疾病的发展，特别关注过敏性和自身免疫性疾病。然后将检查巨噬细胞在炎症消退中的关键作用，强调巨噬细胞清除凋亡免疫细胞的能力。风湿性关节炎（RA）是一种慢性自身免疫驱动的疾病谱，其中持续的炎症导致滑膜增生和过度的免疫细胞积聚，导致受影响关节的重塑和功能降低。巨噬细胞是RA病理生理学的核心，驱动慢性炎症和组织破坏的发作性周期。RA患者具有增加数量的活性M1极化的促炎巨噬细胞和很少或无活性的M2型细胞。巨噬细胞稳态的这种失衡是RA中促炎介质的主要贡献者，导致免疫和基质群体的持续激活和加速组织重塑。巨噬细胞表型和功能的调节仍然是治疗这种疾病的关键治疗目标。有趣的是，糖皮质激素或其他DMARD的治疗干预促进M1巨噬细胞重新极化为抗炎M2表型;这种重编程依赖于代谢变化，以促进表型转换。过敏性哮喘与Th 2极化的气道炎症、大气道的结构重塑和气道高反应性有关。巨噬细胞极化对哮喘发病机制有着深远的影响，因为对过敏原暴露的反应受到局部免疫因子（包括细胞因子、趋化因子和来自邻近细胞的危险信号）之间复杂相互作用的调节。在过敏性哮喘的Th 2极化环境特征中，局部浸润的先天淋巴细胞和辅助性T细胞产生的高水平IL-4促进巨噬细胞获得交替活化的M2 a表型，对局部免疫应答和气道结构具有多种影响。巨噬细胞可塑性的靶向调节剂目前正在寻求治疗过敏性哮喘和其他过敏性疾病。巨噬细胞促进促炎反应向促消退反应的再平衡，因此是炎症反应成功的关键。长期以来已经确定，细胞凋亡支持单核细胞和巨噬细胞募集到炎症部位，促进随后的尸体清除。这驱动了分辨率反应并介导了巨噬细胞极性的表型转换。然而，凋亡细胞衍生的细胞外囊泡（ACdEV）在巨噬细胞表型的募集和控制中的作用却很少受到关注。ACdEV是细胞间通讯的强大介质，携带大量可调节巨噬细胞表型的脂质和蛋白质介质，包括活性免疫调节酶的货物。这种相互作用的影响可能导致不同情况下的修复或疾病。在这篇综述中，我们将讨论无菌炎症性疾病中巨噬细胞的起源，特征和活性，以及通过ACdEV和凋亡细胞清除巨噬细胞极化的潜在机制，以便为可以利用这些敏捷和响应细胞的能力的治疗策略提供新的见解。
Macrophages are dynamic cells that play critical roles in the induction and resolution of sterile inflammation. In this review, we will compile and interpret recent findings on the plasticity of macrophages and how these cells contribute to the development of non-infectious inflammatory diseases, with a particular focus on allergic and autoimmune disorders. The critical roles of macrophages in the resolution of inflammation will then be examined, emphasizing the ability of macrophages to clear apoptotic immune cells. Rheumatoid arthritis (RA) is a chronic autoimmune-driven spectrum of diseases where persistent inflammation results in synovial hyperplasia and excessive immune cell accumulation, leading to remodeling and reduced function in affected joints. Macrophages are central to the pathophysiology of RA, driving episodic cycles of chronic inflammation and tissue destruction. RA patients have increased numbers of active M1 polarized pro-inflammatory macrophages and few or inactive M2 type cells. This imbalance in macrophage homeostasis is a main contributor to pro-inflammatory mediators in RA, resulting in continual activation of immune and stromal populations and accelerated tissue remodeling. Modulation of macrophage phenotype and function remains a key therapeutic goal for the treatment of this disease. Intriguingly, therapeutic intervention with glucocorticoids or other DMARDs promotes the re-polarization of M1 macrophages to an anti-inflammatory M2 phenotype; this reprogramming is dependent on metabolic changes to promote phenotypic switching. Allergic asthma is associated with Th2-polarised airway inflammation, structural remodeling of the large airways, and airway hyperresponsiveness. Macrophage polarization has a profound impact on asthma pathogenesis, as the response to allergen exposure is regulated by an intricate interplay between local immune factors including cytokines, chemokines and danger signals from neighboring cells. In the Th2-polarized environment characteristic of allergic asthma, high levels of IL-4 produced by locally infiltrating innate lymphoid cells and helper T cells promote the acquisition of an alternatively activated M2a phenotype in macrophages, with myriad effects on the local immune response and airway structure. Targeting regulators of macrophage plasticity is currently being pursued in the treatment of allergic asthma and other allergic diseases. Macrophages promote the re-balancing of pro-inflammatory responses towards pro-resolution responses and are thus central to the success of an inflammatory response. It has long been established that apoptosis supports monocyte and macrophage recruitment to sites of inflammation, facilitating subsequent corpse clearance. This drives resolution responses and mediates a phenotypic switch in the polarity of macrophages. However, the role of apoptotic cell-derived extracellular vesicles (ACdEV) in the recruitment and control of macrophage phenotype has received remarkably little attention. ACdEV are powerful mediators of intercellular communication, carrying a wealth of lipid and protein mediators that may modulate macrophage phenotype, including a cargo of active immune-modulating enzymes. The impact of such interactions may result in repair or disease in different contexts. In this review, we will discuss the origin, characterization, and activity of macrophages in sterile inflammatory diseases and the underlying mechanisms of macrophage polarization via ACdEV and apoptotic cell clearance, in order to provide new insights into therapeutic strategies that could exploit the capabilities of these agile and responsive cells.
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影响因子：
7.3
作者：
Alivernini S;Gremese E;McSharry C;Tolusso B;Ferraccioli G;McInnes IB;Kurowska-Stolarska M
通讯作者：
Kurowska-Stolarska M
影响因子：
7.3
作者：
Ariel A;Serhan CN
通讯作者：
Serhan CN
影响因子：
30.5
作者：
Anderson, HA;Maylock, CA;Shacter, E
通讯作者：
Shacter, E
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.7
作者：
Alessandri AL;Duffin R;Leitch AE;Lucas CD;Sheldrake TA;Dorward DA;Hirani N;Pinho V;de Sousa LP;Teixeira MM;Lyons JF;Haslett C;Rossi AG
通讯作者：
Rossi AG