Pancreatitis is associated with dendritic cell expansion and migration to pancreas-associated lymphoid tissue and increased effector T cell output.

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B542
Abstract ID: 5563

Presenting Author:
Aoife Young , Staff Associate I at Columbia Univ. Irving Med. Ctr.

Abstract:

In chronic pancreatitis (CP), repeated episodes of pancreatic damage provoke a fibroinflammatory reaction leading to pancreatic insufficiency and severe pain. T cells infiltrate and promote tissue destruction in CP, but the mechanisms of T cell mobilization from lymphoid tissues and the role of antigen presenting cells (APCs) are poorly understood. Here we used flow cytometry to examine how CP shapes APC populations and trafficking across pancreas-associated tissues from 6 CP patients and 13 organ donor controls. In CP there were significant increases in plasmacytoid and conventional dendritic cells (pDCs, cDCs) across pancreas lymph node (PLN), spleen (SPL), and blood (BL), but not duodenum (DUO). Migratory DCs (migDCs) with high expression of the lymph node homing receptor, CCR7, were elevated in PLN of CP patients. Compared to other tissues, the migDCs within PLN showed the highest expression of MHC-II and the co-stimulation molecules CD86 and CD40. In conjunction with this altered APC landscape, we observed changes in PLN T cell effector states. In CP, CD8 T cells showed upregulation of T- bet, and we found higher numbers of memory CD4 TH1 (T-BET⁺), and TH17 (RORgt⁺) cells that express CCR6. Increased CD4 T regulatory cells (FOXP3⁺ CD127^- CD25⁺) were also found in PLN during CP. Together, these results suggest that DC accumulation in and migration to lymphoid tissue during CP may boost output of effector and regulatory T cells targeting the inflamed pancreas.