Golden Gregory J, Wu Vincent H, Hamilton Jacob T, Amses Kevin R, Shapiro Melanie R, Sada Japp Alberto, Liu Chengyang, Pampena M Betina, Kuri-Cervantes Leticia, Knox James J, Gardner Jay S, Atkinson Mark A, Brusko Todd M, Luning Prak Eline T, Kaestner Klaus H, Naji Ali, Betts Michael R
Department of Microbiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Institute for Immunology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Nat Commun. 2025 May 18;16(1):4621. doi: 10.1038/s41467-025-59626-0.
Autoimmune destruction of pancreatic β cells results in type 1 diabetes (T1D), with pancreatic immune infiltrate representing a key feature in this process. However, characterization of the immunological processes occurring in human pancreatic lymphatic tissues is lacking. Here, we conduct a comprehensive study of immune cells from pancreatic, mesenteric, and splenic lymphatic tissues of non-diabetic control (ND), β cell autoantibody-positive non-diabetic (AAb+), and T1D donors using flow cytometry and CITEseq. Compared to ND pancreas-draining lymph nodes (pLN), AAb+ and T1D donor pLNs display decreased CD4+ Treg and increased stem-like CD8+ T cell signatures, while only T1D donor pLNs exhibit naive T cell and NK cell differentiation. Mesenteric LNs have modulations only in CD4+ Tregs and naive cells, while splenocytes lack these perturbations. Further, T cell expression of activation markers and IL7 receptor correlate with T1D genetic risk. These results demonstrate tissue-restricted immune changes occur before and after T1D onset.
胰腺β细胞的自身免疫性破坏会导致1型糖尿病（T1D），胰腺免疫浸润是这一过程的关键特征。然而，目前缺乏对人类胰腺淋巴组织中发生的免疫过程的特征描述。在此，我们使用流式细胞术和CITEseq对非糖尿病对照（ND）、β细胞自身抗体阳性非糖尿病（AAb+）和T1D供体的胰腺、肠系膜和脾脏淋巴组织中的免疫细胞进行了全面研究。与ND胰腺引流淋巴结（pLN）相比，AAb+和T1D供体的pLN显示CD4+调节性T细胞减少，干细胞样CD8+T细胞特征增加，而只有T1D供体的pLN表现出初始T细胞和自然杀伤细胞分化。肠系膜淋巴结仅在CD4+调节性T细胞和初始细胞中有调节变化，而脾细胞则没有这些扰动。此外，T细胞激活标志物和IL7受体的表达与T1D遗传风险相关。这些结果表明，在T1D发病前后会发生组织特异性的免疫变化。
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