# Peripheral mechanisms of homeostasis and tolerance through skin dendritic cells

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $455,723

## Abstract

Project Summary/Abstract
The immune system surveys the skin and other barrier tissues such as lung and gut, but
mechanisms for failed immunity in the periphery that lead to cancer or autoimmune diseases
are unknown. The dendritic cell (DC) is a specialized immune sentinel that directs T cells to
tolerance or immunity. DC comprise a rich network in skin consisting of several different
populations, but are understudied, leaving a major gap in therapeutic intervention. We have
identified distinct properties for DC in skin that relay information by migrating out to the draining
lymph node (LN). We find during inflammation skin migratory DC may direct T cells to tolerance
by unknown mechanisms, counter-regulating and controlling immunity. These cells are uniquely
genetically programed in humans and in mouse to dampen immunity with a high expression of
shared tolerance genes, including some genes such as PD-L1 that have been successfully
targeted in the clinic for peripheral tissue cancers including melanoma skin cancer, colorectal
cancer and lung cancer. We hypothesize homeostatic programming of skin DC leads to failed
immune priming leading to impaired early detection of skin cancers. We find these pathways are
of great importance as therapeutic targets to promote self-tolerance (such as during
autoimmune disease) or to block tolerance (to improve immunity during cancer). Because these
mechanisms are distinct they can be combined with current modalities for patients in
immunotherapy of skin cancer, vaccine science, and inflammatory skin disease. In 2 discrete
aims, this application will address programmatic conditioning of skin DCs and the unique cellular
mechanisms by which they promote immune tolerance in both mice and humans, examining
consequences during immune priming and early skin cancer growth.

## Key facts

- **NIH application ID:** 10004498
- **Project number:** 5R01AR070234-06
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Niroshana Anandasabapathy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $455,723
- **Award type:** 5
- **Project period:** 2018-04-11 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004498

## Citation

> US National Institutes of Health, RePORTER application 10004498, Peripheral mechanisms of homeostasis and tolerance through skin dendritic cells (5R01AR070234-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10004498. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*