# PD-L1 reverse signaling in dermal DCs promotes DC migration and skin immunity to cutaneous pathogens

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $452,434

## Abstract

Project Summary
The goal of this proposal is to identify the mechanism(s) by which PD-L1 reverse signaling in dendritic cells
(DC) initiates DC trafficking, T cell priming and T cell programming during cutaneous infection. Our studies
have outlined a major role for PD-L1 reverse signaling in the control of DC migration from the skin to the
draining lymph node. Intriguingly, this loss of migration appears to be dependent on TLR stimulation or
infections that initiate type 1 IFN signaling. These findings are consistent with PD-L1 acting to mitigate type 1
IFN signaling events. We also outline a requirement for PD-L1 reverse signaling in chemokine, but not S1P,
responsiveness demonstrating a new role for PD-L1 in regulating chemokine signaling. Finally, we find T cell
priming in the lymph node is significantly decreased in the absence of PD-L1 reverse signaling. However,
these defects in T cell priming only occur when DC trafficking is required, and not when antigens drain directly
through the lymphatics and to the LN nor following systemic infection. Therefore, in this proposal we aim to
better understand the requirements for PD-L1 reverse signaling in dendritic cell transmigration through the
lymphatic capillaries. We also aim to understand how the extracellular and intracellular domains of PD-L1 may
control responsiveness to chemokines. Finally, we aim to address the contribution of DC retention in the skin
caused by loss of PD-L1 signaling to tissue resident memory responses established after vaccinia scarification.

## Key facts

- **NIH application ID:** 10267698
- **Project number:** 5R01AI155474-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Beth Ann Tamburini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $452,434
- **Award type:** 5
- **Project period:** 2020-09-21 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267698

## Citation

> US National Institutes of Health, RePORTER application 10267698, PD-L1 reverse signaling in dermal DCs promotes DC migration and skin immunity to cutaneous pathogens (5R01AI155474-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10267698. Licensed CC0.

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