# Transitional dendritic cells: identifying the origin and role of a novel innate immune population during viral infection

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $560,551

## Abstract

ABSTRACT
Plasmacytoid dendritic cells (pDCs) are a unique subset of innate immune cells capable of multiple functions
essential for antiviral responses, including type I interferon production, antigen-presentation and T cell activation.
The mechanisms that govern these distinct pDC functions remain poorly defined; however, they could be
mediated by distinct subpopulations. Using high-dimensional single-cell proteomic and transcriptomic
approaches, we and others recently discovered a novel human dendritic cell (DC) population that is captured
within traditional pDC definitions. These cells harbor phenotypic features of both pDCs and conventional DC
subsets (cDCs); thus, we called them transitional DCs or tDCs. We have now performed an integrated
multidimensional comparison that resulted in the identification of the mouse homolog of human tDCs. The
discovery that tDCs occur in both human and mouse suggests they have an evolutionarily conserved role during
immune responses. However, tDC function has never been investigated. Similarly, the developmental origin of
tDCs has not yet been analyzed. This represents a fundamental gap in our understanding of the cellular
components that mediate innate immune responses against viruses and poses an impediment to the
development of therapeutics. Based on our preliminary data generated in mouse, we hypothesize that tDCs and
pDCs form a distinct developmental lineage that cooperates at the site of viral infection to modulate immune
responses. In three specific aims, we propose to query tDC origin, function and relationship with pDCs. To
achieve these aims, we will take advantage of high-dimensional approaches already established in our lab, in
vitro and in vivo differentiation assays, and novel lineage tracing and cell-specific depletion mouse models. We
anticipate that findings from this proposal will enhance our current understanding of innate cellular pathways that
result in the positive outcome of viral infection. Importantly, our integrated approach will incorporate analyses of
both mouse and human tDCs; thus, it has the potential to reveal features of the innate immune compartment
that are conserved between species. This proposal has the potential to impact the rational design of future
therapeutic strategies.

## Key facts

- **NIH application ID:** 10350705
- **Project number:** 5R01AI158808-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Juliana Idoyaga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $560,551
- **Award type:** 5
- **Project period:** 2021-02-12 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350705

## Citation

> US National Institutes of Health, RePORTER application 10350705, Transitional dendritic cells: identifying the origin and role of a novel innate immune population during viral infection (5R01AI158808-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10350705. Licensed CC0.

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