# Mechanism of cDC2 subset differentiation in peripheral organs

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $748,311

## Abstract

Project Summary
Conventional dendritic cells (cDCs) are crucial for both innate and adaptive immunity. In general, cDCs can be
categorized roughly into two functionally and developmentally distinct subsets, cDC1 and cDC2, which
preferentially activate CD8T cells and CD4T cells, respectively. cDC2s are phenotypically and functionally
more heterogeneous compared to cDC1s, but how different cDC2 subsets acquire distinct phenotype and
function remains poorly understood. We previously showed that a mouse cDC2 subset expressing CD301b
(Mgl2) is functionally distinct and plays critical role in type 2 immune responses to allergens and helminth
parasites. CD301b+ DCs are present in nearly all peripheral organs and expand during type 2 inflammation, but
their differentiation mechanism is unknown. Our long-term goal is to understand the mechanism of CD301b+
DC differentiation at the cellular and molecular levels and explore its potential as a therapeutic targets for
diseases with type 2 inflammation such as allergies. In general, cDC2s are thought to originate from the pre-
cDC, a cDC-committed circulating precursor, through the action of the transcription factor IRF4. However, it
remains unclear whether the heterogeneity in cDC2s originates in their precursors, or is acquired later during
terminal differentiation. Likewise, while IRF4 seems to play a significant role in cDC2 development in general,
its role in diversification of cDC2 subsets remains elusive and additional factors may be responsible for their
heterogeneity. We hypothesize that pre-cDCs and/or monocytes acquire the CD301b+ DCs phenotype in a
context-dependent manner with context-dependent requirement of IRF4. Our specific aims in this proposal are
(1) to identify the precursor cell populations that give rise to CD301b+ DCs in peripheral organs, and (2) to
elucidate the role of IRF4 and CD301b+ DC-specific transcription factors in their differentiation, under both
naive and infected conditions. Understanding the mechanism of cDC2 differentiation might give us clues to
understand the etiology and to identify potential therapeutic targets in allergies and other diseases with type 2
inflammation.

## Key facts

- **NIH application ID:** 10862708
- **Project number:** 5R01AI165622-02
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** YOSUKE KUMAMOTO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $748,311
- **Award type:** 5
- **Project period:** 2023-06-08 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862708

## Citation

> US National Institutes of Health, RePORTER application 10862708, Mechanism of cDC2 subset differentiation in peripheral organs (5R01AI165622-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10862708. Licensed CC0.

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