# Regulation of Innate Dendritic Cell CTLA-4

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $396,250

## Abstract

Abstract
The promise of harnessing cell-mediated (TH1) immunity to treat cancer or establish prophylactic immunity
against chronic viral pathogens like HIV continues to be hampered by an incomplete understanding of many
different critical factors and processes, including the manner by which the innate and adaptive immune 
systems interface and communicate. CTLA-4 is one of the best characterized of the immune checkpoint proteins,
molecules that serve to balance, regulate, and fine-tune immune activation with homeostatic inhibition. The
critical importance of CTLA-4 to the regulation of T-cell activation and proliferation was demonstrated nearly
two decades ago by the dramatic phenotype of the null mutant, animals which die in the early postnatal period
of uncontrolled lymphoproliferation and autoimmune inflammation. CTLA-4 is expressed by all major lymphoid
lineage effectors including T, B, and NK cells; however, its functionality has been best characterized in T-cells
where it exhibits both cell-extrinsic and cell-intrinsic regulatory functions. There is almost nothing known about
CTLA-4 expression or function in non-lymphoid cell types, and sporadic reports of CTLA-4 expression in non-
lymphoid lineages have been inconclusive. Recently our group reported expression and secretion of 
microvesicle-bound CTLA-4 from myeloid lineage innate dendritic cells (DC). Microvesicular CTLA-4 
demonstrat
ed the ability to bind B7, leading to vesicle internalization and subsequent downregulation of B7 expression.
Knockdown of DC-expressed CTLA-4 resulted in a dramatic upregulation of CD8+ cell proliferation as well as
enhanced antitumor and antiviral immunity in vivo. The discovery of non-lymphoid CTLA-4 expression in an
innate cell type and concomitant characterization of novel function signifies a significant paradigm shift in the
understanding of CTLA-4's role in immune governance as well as the manner by which the innate and adaptive
arms of the immune system communicate. Successful completion of the work proposed herein will characterize
the basic mechanisms by which DC expressed CTLA-4 is regulated as well as the manner by which this critical
immunoregulatory molecule contributes to crosstalk between innate and adaptive immunity. These data will
enable and accelerate development of novel therapeutic approaches and assist in enhanced exploitation of
existing therapeutics (i.e. ipilimumab) that target CTLA-4 checkpoint pathways.

## Key facts

- **NIH application ID:** 10102169
- **Project number:** 5R01AI127387-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** WILLIAM Karl DECKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2017-03-13 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102169

## Citation

> US National Institutes of Health, RePORTER application 10102169, Regulation of Innate Dendritic Cell CTLA-4 (5R01AI127387-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10102169. Licensed CC0.

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