# Regulation of the development of dendritic cells in barrier tissues by retinoid gradients

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $226,767

## Abstract

PROJECT SUMMARY
Langerin-expressing dendritic cell (DC) subsets function as immunological sentinels and either activate or
regulate immune responses to pathogens and tumor cells. Their importance in the immune system has
been established, for example, by the role of Langerhans cells (LCs) in blocking HIV pathogenesis and the
role of langerin+ DCs in mounting effector T cell responses to other pathogens. Langerin+ DCs have
unique tissue tropism or distribution: LCs are present in the epithelial layer of the skin and mucosal
tissues, such as oral, lung, vaginal and intestinal tissues, while other langerin+ DCs are found in the
dermal layer and throughout lymphoid and non-lymphoid tissues at low frequencies. There is a significant
gap in our understanding of the mechanisms by which the development of these specialized DC subsets is
regulated in a tissue-dependent manner. We hypothesize that vitamin A, retinoic acid, and their receptors
are key regulators of the development and tissue tropism of most langerin-expressing DCs, regulating the
specialized DCs in a manner similar to their roles in regulating embryo morphogenesis by providing spatial
cues to developing precursor cells. The overall goal of this project is to establish the roles of retinoic acid-
RAR axis in the regulation of langerin+ DC populations. To test this hypothesis and attain the defined
goal, we will determine the role of RAR as a transcription factor necessary for tissue-specific
development of langerin-expressing DC subsets and will study the function of retinoic acid as a negative
regulator to limit ectopic development of langerin-expressing DC subsets. The proposed research will
identify fundamental functions of vitamin A metabolites and their receptors in regulating langerin-
expressing DC subsets. The outcomes are expected to provide novel information regarding the tissue-
specific development of langerin-expressing DC subsets. The outcomes will provide novel ideas to
maintain effective immunity and to control inflammatory responses mediated by the specialized DC
subsets.

## Key facts

- **NIH application ID:** 9873596
- **Project number:** 1R21AI148898-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** CHANG H KIM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $226,767
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873596

## Citation

> US National Institutes of Health, RePORTER application 9873596, Regulation of the development of dendritic cells in barrier tissues by retinoid gradients (1R21AI148898-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873596. Licensed CC0.

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