Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?
Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?
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DOI：
10.3389/fimmu.2012.00147
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发表时间：
2012
影响因子：
7.3
通讯作者：
Hatfield JK
中科院分区：
文献类型：
--
作者：
Brown MA;Hatfield JK
有大量证据表明，肥大细胞是自身免疫性疾病中介导组织损伤的事件的积极参与者。在包括多发性硬化症、类风湿性关节炎和大疱性类天疱疮在内的许多人类自身免疫性疾病中，通常可以观察到疾病相关的肥大细胞数量增加，伴随着肥大细胞脱颗粒和炎症部位大量肥大细胞介质的形成。在动物模型中，使用肥大细胞稳定剂或肥大细胞消融治疗可以减少疾病。包括抗体、补体、病原体和内在危险信号在内的多种受体参与了疾病中肥大细胞的激活。与在感染环境中作为第一反应者的角色类似，肥大细胞可能会协调包括中性粒细胞在内的免疫细胞早期招募到自身免疫破坏的部位。这种共定位促进了细胞的串扰和激活，并导致局部炎症反应的放大，从而促进和维持组织损伤。尽管有证据，但关于肥大细胞在这些过程中的相对作用仍存在争议。然而，根据定义，肥大细胞只能作为自身反应性T细胞和/或抗体驱动的自身免疫反应的辅助细胞。因此，当使用现有的和有些不完善的疾病动物模型评估肥大细胞参与时，它们的重要性有时被掩盖。然而，这些强大的免疫细胞无疑是自身免疫的主要贡献者，应被视为治疗性疾病干预的重要靶点。
There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1196/annals.1422.059
发表时间：
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期刊：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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