Department of Pathology, University of Chicago, Chicago, IL, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Institute of Infection, Inflammation, and Immunity, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
Immunity. 2023 Sep 12;56(9):2070-2085.e11. doi: 10.1016/j.immuni.2023.07.008. Epub 2023 Aug 8.
Lymph nodes (LNs) are critical sites for shaping tissue-specific adaptive immunity. However, the impact of LN sharing between multiple organs on such tailoring is less understood. Here, we describe the drainage hierarchy of the pancreas, liver, and the upper small intestine (duodenum) into three murine LNs. Migratory dendritic cells (migDCs), key in instructing adaptive immune outcome, exhibited stronger pro-inflammatory signatures when originating from the pancreas or liver than from the duodenum. Qualitatively different migDC mixing in each shared LN influenced pancreatic β-cell-reactive T cells to acquire gut-homing and tolerogenic phenotypes proportional to duodenal co-drainage. However, duodenal viral infections rendered non-intestinal migDCs and β-cell-reactive T cells more pro-inflammatory in all shared LNs, resulting in elevated pancreatic islet lymphocyte infiltration. Our study uncovers immune crosstalk through LN co-drainage as a powerful force regulating pancreatic autoimmunity.
淋巴结 (LNs) 是塑造组织特异性适应性免疫的关键部位。然而，LN 在多个器官之间的共享对这种适应性的影响还不太清楚。在这里，我们描述了胰腺、肝脏和上部小肠（十二指肠）引流到三个小鼠 LN 的顺序。迁移树突状细胞 (migDC) 是指导适应性免疫结果的关键细胞，当它们来源于胰腺或肝脏时，比来源于十二指肠时表现出更强的促炎特征。每种共享 LN 中存在的 migDC 混合的质量不同，会影响胰腺 β 细胞反应性 T 细胞获得肠道归巢和耐受表型，与十二指肠共同引流成比例。然而，十二指肠的病毒感染使非肠道 migDC 和 β 细胞反应性 T 细胞在所有共享的 LN 中更具促炎作用，导致胰腺胰岛淋巴细胞浸润增加。我们的研究揭示了 LN 共同引流的免疫串扰是调节胰腺自身免疫的强大力量。
