Type 1 diabetes mellitus (T1DM) is an autoimmune disease that targets the destruction of islet beta-cells resulting in insulin deficiency, hyperglycemia and death if untreated. Despite advances in medical devices and longer-acting insulin, there is still no robust therapy to substitute and protect beta-cells that are lost in T1DM. Attempts to refrain from the autoimmune attack have failed to achieve glycemic control in patients highlighting the necessity for a paradigm shift in T1DM treatment. Paradoxically, beta-cells are present in T1DM patients indicating a disturbed equilibrium between the immune attack and beta-cell regeneration reminiscent of unresolved wound healing that under normal circumstances progression towards an anti-inflammatory milieu promotes regeneration. Thus, the ultimate T1DM therapy should concomitantly restore immune self-tolerance and replenish the beta-cell mass similar to wound healing. Recently the agonistic activation of the nuclear receptor LRH-1/NR5A2 was shown to induce immune self-tolerance, increase beta-cell survival and promote regeneration through a mechanism of alpha-to-beta cell phenotypic switch. This trans-regeneration process appears to be facilitated by a pancreatic anti-inflammatory environment induced by LRH-1/NR5A2 activation. Herein, we review the literature on the role of LRH1/NR5A2 in immunity and islet physiology and propose that a cross-talk between these cellular compartments is mandatory to achieve therapeutic benefits.

中文翻译：

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治疗1型糖尿病的模式转变时间：将炎症与胰岛再生结合起来。

1型糖尿病（T1DM）是一种自身免疫性疾病，其目标是破坏胰岛β细胞，导致胰岛素缺乏，高血糖症和未经治疗而死亡。尽管医疗设备和长效胰岛素取得了进步，但仍没有可靠的疗法来替代和保护在T1DM中丢失的β细胞。避免自身免疫攻击的尝试未能在患者中实现血糖控制，突显了在T1DM治疗中需要转变范例。矛盾的是，T1DM患者中存在β细胞，这表明免疫攻击和β细胞再生之间的平衡紊乱，使人想起未解决的伤口愈合，在正常情况下，这种情况会发展为消炎环境，从而促进再生。从而，最终的T1DM治疗应与伤口愈合类似，同时恢复免疫自耐受并补充β细胞。最近，核受体LRH-1 / NR5A2的激动性激活可诱导免疫自耐受，增加β细胞存活并通过α至β细胞表型转换机制促进再生。由LRH-1 / NR5A2激活诱导的胰腺抗炎环境似乎促进了这种转生过程。本文中，我们回顾了有关LRH1 / NR5A2在免疫和胰岛生理中的作用的文献，并提出在这些细胞区室之间进行串扰对于实现治疗益处是必不可少的。最近，核受体LRH-1 / NR5A2的激动性激活可诱导免疫自耐受，增加β细胞存活并通过α至β细胞表型转换机制促进再生。由LRH-1 / NR5A2激活诱导的胰腺抗炎环境似乎促进了这种转生过程。本文中，我们回顾了有关LRH1 / NR5A2在免疫和胰岛生理中的作用的文献，并提出在这些细胞区室之间进行串扰对于实现治疗益处是必不可少的。最近，核受体LRH-1 / NR5A2的激动性激活可诱导免疫自耐受，增加β细胞存活并通过α至β细胞表型转换机制促进再生。由LRH-1 / NR5A2激活诱导的胰腺抗炎环境似乎促进了这种转生过程。本文中，我们回顾了有关LRH1 / NR5A2在免疫和胰岛生理中的作用的文献，并提出在这些细胞区室之间进行串扰对于实现治疗益处是必不可少的。