| First Author | Brown H | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 9 | Pages | 2070-2085.e11 |
| PubMed ID | 37557168 | Mgi Jnum | J:340614 |
| Mgi Id | MGI:7528595 | Doi | 10.1016/j.immuni.2023.07.008 |
| Citation | Brown H, et al. (2023) Lymph node sharing between pancreas, gut, and liver leads to immune crosstalk and regulation of pancreatic autoimmunity. Immunity 56(9):2070-2085.e11 |
| abstractText | 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 beta-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 beta-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. |
