# Tissue Resident Immune Cells in Human Pancreas.

> **NIH NIH K08** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $165,456

## Abstract

PROJECT SUMMARY ABSTRACT
Dr. Weisberg is a Clinical Pathologist and Physician Scientist investigating the unique immune
microenvironment within human pancreas. Immune regulation within tissues is highly dependent on non-
recirculating resident immune cells. Tissue macrophages modulate local immune function, sense metabolic
disturbances and participate in tissue repair and homeostasis, and tissue resident memory T cells (Trm)
provide localized protective immune responses and tissue immune surveillance. Populations of Trm have now
been identified in almost all tissues of the body. Human and murine studies show that Trm are phenotypically,
transcriptionally and functionally distinct compared to circulating T cells. Although core properties of Trm
common to most tissue sites have been identified, the differentiation state and functional profiles of Trm are
also shaped by their microenvironment. These tissue specific properties of Trm and how they are altered by
local stressors are less well defined. Due to the limited availability of healthy human pancreas tissue, relatively
little is known about the resident immune cells of human pancreas. More knowledge is needed about these
cells, because disruption of pancreatic immune homeostasis has severe consequences for human health,
leading to diseases with high morbidity and mortality including acute and chronic pancreatitis, type I diabetes
and pancreatic cancer. Obesity is associated with pro-inflammatory changes in pancreas and is a major risk
factor for pancreatitis and pancreatic cancer. Elucidating the mechanisms that regulate pancreas resident
immune cells and how they are influenced by metabolic stressors such as obesity may suggest novel
strategies to prevent and treat pancreatic disease. Using a resource within Dr. Donna Farber’s lab which
provides access to multiple gastrointestinal tissues from previously healthy organ donors, our preliminary
studies have already defined several unique properties of pancreatic Trm. Within pancreas, networks of CD8
Trm cluster with macrophages in the exocrine and ductal areas, surrounding but not penetrating into the
endocrine islets. The Trm are resting but with high functional capacity, and the macrophages express
mediators of both positive and negative T cell regulation. Our central hypothesis is that pancreatic Trm are
maintained in a state distinct from other sites by their local interactions with pancreatic macrophages; and due
to their residence in a key tissue that regulates and senses metabolic changes, pancreatic Trm are uniquely
sensitive to metabolic alterations such as obesity. The aims of the proposal are 1) Define the distinct properties
of Trm in pancreas compared to neighboring tissues; 2) Identify mechanisms of pancreatic Trm-macrophage
crosstalk; 3) Identify obesity-related changes in pancreas Trm functional profiles and localization. This career
development award will provide critical training and experience in human T cell immunology researc...

## Key facts

- **NIH application ID:** 10436284
- **Project number:** 5K08DK122130-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Stuart P Weisberg
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $165,456
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436284

## Citation

> US National Institutes of Health, RePORTER application 10436284, Tissue Resident Immune Cells in Human Pancreas. (5K08DK122130-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10436284. Licensed CC0.

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