| First Author | Zhou YD | Year | 2026 |
| Journal | Cell Rep | Volume | 45 |
| Issue | 5 | Pages | 117324 |
| PubMed ID | 42090287 | Mgi Jnum | J:385369 |
| Mgi Id | MGI:8331421 | Doi | 10.1016/j.celrep.2026.117324 |
| Citation | Zhou YD, et al. (2026) Tissue-specific tolerance mechanisms and lymph node co-drainage shape T cell immunity in the upper digestive system and pancreatic cancer progression. Cell Rep 45(5):117324 |
| abstractText | The liver, pancreas, and duodenum share lymph nodes (LNs), providing a unique system to examine how tissue origin of self-antigens shapes T cell fate. Comparing mice expressing ovalbumin (OVA) from distinct subcellular compartments, we found that cytosolic OVA from the liver or pancreas, but not gut, was immunologically ignored. High-dose hepatic-secreted OVA triggered antigen-specific T cell deletion, whereas secreted pancreatic and intestinal OVA induced regulatory T (Treg) cells, revealing immunological ignorance, clonal deletion, and Treg cell generation as tissue-specific tolerance mechanisms. Of these, LN co-drainage only influenced Treg cell induction, establishing gut-pancreas-liver axes: intestinal viral infection rendered hepatocyte- and exocrine pancreas-specific T cells inflammatory and liver injury promoted pancreas- and gut-directed responses. These self-reactive T cells caused tissue destruction but enhanced pancreatic tumor control when neoantigen OVA was secreted, but not cytosolic. Thus, LN co-drainage and tissue-specific tolerance mechanisms jointly shape immune homeostasis and disease susceptibility in the upper digestive system. |
