Insulitis in the pathogenesis of type 1 diabetes.
Insulitis in the pathogenesis of type 1 diabetes.
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DOI：
10.1111/pedi.12388
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Pugliese A
中科院分区：
文献类型：
--
作者：
Pugliese A
1型糖尿病（T1 D）是一种慢性自身免疫性疾病，其中自身反应性T细胞和炎症导致胰腺β细胞严重损失。胰岛炎是T1 D的病理标志，是由胰岛周围和内部的免疫细胞浸润组成的炎性病变。新的研究举措和方法正在推进我们对胰腺病理学的理解。研究揭示了浸润胰岛的主要细胞类型、与胰岛炎相关的新分子方面以及其他病理异常的共存。虽然胰岛炎是T1 D病理学和发病机制的关键要素，但它通常在任何给定时间仅存在于适度比例的胰岛中，即使在诊断时也是如此，与疾病持续时间的关系总体上有限。因此，胰岛炎作为疾病发作时糖尿病症状的决定因素的相对重要性似乎被高估了;越来越多的证据也表明，诊断时β细胞的损失比以前认为的要小。因此，如果功能障碍影响不受免疫攻击的β细胞，则免疫系统的唯一靶向可能无法提供完全的治疗功效，并且这是症状的关键因素。促进免疫调节和解决β细胞功能障碍的联合疗法在治疗这种慢性疾病过程中应该更有效。它仍然是一个主要的目标，以澄清胰岛炎的β细胞损失的动态和功能障碍的共存机制，根据临床阶段的关系;这种改善的理解是设计治疗策略的关键，针对多种致病机制。
Type 1 diabetes (T1D) is a chronic autoimmune disease in which autoreactive T‐cells and inflammation cause severe loss of pancreatic beta cells. Insulitis, the pathologic hallmark of T1D, is an inflammatory lesion consisting of immune cell infiltrates around and within the islets. New research initiatives and methodologies are advancing our understanding of pancreas pathology. Studies have revealed the predominant cellular types that infiltrate the islets, novel molecular aspects associated with insulitis, and the coexistence of additional pathological abnormalities. While insulitis is a critical element of T1D pathology and pathogenesis, it is typically present only in a modest proportion of islets at any given time, even at diagnosis, with overall limited relation to disease duration. Thus, the relative importance of insulitis as a determining factor of diabetes symptoms at disease onset appears to have been overestimated; growing evidence also shows that beta cell loss at diagnosis is more modest than previously thought. Thus, the sole targeting of the immune system may not afford full therapeutic efficacy if dysfunction affects beta cells that are not under immune attack and this is a key contributor to symptoms. Combination therapies that promote both immunoregulation and address beta cell dysfunction should be more effective in treating this chronic disease process. It remains a major goal to clarify the relation of insulitis with the dynamics of beta cell loss and coexisting mechanisms of dysfunction, according to clinical stage; such improved understanding is key to design therapeutic strategies that target multiple pathogenic mechanisms.