# Role of the local vascular microenvironment in the bone marrow response to inflammation

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $568,892

## Abstract

Abstract:
Bone marrow (BM) inflammation is a driver of hematopoietic stem and progenitor cell (HSPC) aging,
transformation, and marrow failure but also indispensable for innate immune responses to infection. The role of
the microenvironment in the response to inflammation is incompletely understood. We found that unique
subsets of marrow vessels differentially regulate neutrophil or dendritic cell production in respond to
inflammation. We want to understand how the local architecture of the microenvironment controls which –and
how- HSPC respond to infection/inflammation.
We have found that CSF1+ vessels regulate emergency dendritic cell production in response to infection by
targeting myeloid dendritic cell progenitors (MDP) whereas IL1R1+ vessels regulate multipotent progenitors
and committed granulocyte progenitors in response to IL1. We hypothesize “that the local architecture of the
BM vascular microenvironment controls which-and how- HSPC respond to infection/inflammation. Unique
subsets of BM vessels are cellular antennas that sense different inflammatory insults and control commitment
and differentiation of adjacent HSPC in response to these insults. IL1R1+ and CSF1+ vessels are two
examples of these cellular antennas”
We will test this hypothesis in three aims. In Aim 1 we will investigate how the different vessels spatially
organize hematopoiesis and test the hypothesis that proximity to each vessel dictates which progenitor
responds to infection/inflammation. In Aim2 we will investigate the mechanisms through which each type of
vessel regulates HSPSC function and differentiation. In Aim 3 we will determine how each type of vessel
senses and responds to different types of infection/inflammation and test the hypothesis that each vessel has
evolved to sense specific insults.

## Key facts

- **NIH application ID:** 10273567
- **Project number:** 1R01HL158616-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Daniel Lucas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $568,892
- **Award type:** 1
- **Project period:** 2021-07-20 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10273567

## Citation

> US National Institutes of Health, RePORTER application 10273567, Role of the local vascular microenvironment in the bone marrow response to inflammation (1R01HL158616-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10273567. Licensed CC0.

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