胰岛外胰腺支持人类 1 型糖尿病的自身免疫功能

G L Barlow, C M Schürch, S S Bhate, D Phillips, A Young, S Dong, H A Martinez, G Kaber, N Nagy, S Ramachandran, J Meng, E Korpos, J A Bluestone, G P Nolan, P L Bollyky
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摘要

在自身免疫性 1 型糖尿病(T1D)中,免疫细胞会浸润并破坏朗格汉斯胰岛--分散在整个胰腺中的内分泌组织岛。然而,胰岛外的细胞程序对胰岛炎的影响尚不清楚。在这里,我们利用 CO-Detection by indEXing (CODEX) 组织成像和尸体胰腺样本,同时研究了人类 T1D 中的胰岛和胰岛外炎症。我们发现了四种胰岛炎症亚状态,其特点是胰岛中的 CD8 + T 细胞活化图谱相对于周围组织更为丰富。我们进一步发现,在同一组织切片中,胰岛广泛浸润的小叶的胰岛外空间与浸润较少区域的胰岛外空间不同。最后,我们发现远离胰岛的淋巴结构富含 CD45RA + T 细胞--这也是胰岛发炎亚状态之一的富集人群。这些数据有助于确定胰岛和胰岛外胰腺在人类 T1D 发病机制中的协调作用。
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The Extra-Islet Pancreas Supports Autoimmunity in Human Type 1 Diabetes.

In autoimmune Type 1 diabetes (T1D), immune cells infiltrate and destroy the islets of Langerhans - islands of endocrine tissue dispersed throughout the pancreas. However, the contribution of cellular programs outside islets to insulitis is unclear. Here, using CO-Detection by indEXing (CODEX) tissue imaging and cadaveric pancreas samples, we simultaneously examine islet and extra-islet inflammation in human T1D. We identify four sub-states of inflamed islets characterized by the activation profiles of CD8 + T cells enriched in islets relative to the surrounding tissue. We further find that the extra-islet space of lobules with extensive islet-infiltration differs from the extra-islet space of less infiltrated areas within the same tissue section. Finally, we identify lymphoid structures away from islets enriched in CD45RA + T cells - a population also enriched in one of the inflamed islet sub-states. Together, these data help define the coordination between islets and the extra-islet pancreas in the pathogenesis of human T1D.

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