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A Vascular Antenna Senses Inflammation and Orchestrates Emergency Granulopoiesis in the Bone Marrow

Slaughter, Anastasiya
http://orcid.org/0000-0003-4414-3639
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1703168877684916

Abstract Details

2023, PhD, University of Cincinnati, Medicine: Immunology.
The bone marrow (BM) is a hematopoietic (blood forming) organ that dynamically adjusts output to accommodate demand. Hematopoietic stem and progenitor cells (HSPC) reside within the BM and sequentially differentiate to feed each major lineage. All lineages are derived from the hematopoietic stem cells (HSC). HSC give rise to erythroid progenitors that terminally differentiate into red blood cells (RBC); lymphoid progenitors that generate dendritic cells (DC), B and T-cells that provide long term adaptive immunity; and myeloid progenitors that give rise to granulocytes, monocytes and macrophages which coordinate the rapid innate immune responses. These progenitors inhabit a network of non-hematopoietic (stromal) cells that maintain and regulate progenitors. Different tissue cells comprise the stromal cell compartment, including endothelial cells that make up vessels, osteoblasts that make up bone, fat cells, nerve cells, and perivascular stromal cells which are derived from mesenchymal stem cells (MSC). Stromal cells provide essential retention and differentiation cues, whose function depends on the cellular source of these cytokines. Besides stromal cells, mature hematopoietic cells can also directly and indirectly regulate hematopoietic progenitors. Together, the combination of stromal and hematopoietic cells, along with their cytokine products, make up spatially distinct niches in the BM. Acute and chronic insults can lead to inflammation which dramatically changes BM output. The subsequent cytokine storm can regulate progenitors directly or indirectly via a stromal cell intermediary. While inflammatory responses are advantageous to pathogen clearance, in other cases, inflammation leads to reprogramming of progenitors and BM output. When inflammation is sensed by progenitors, they become activated, proliferate, mobilize, or terminally differentiate into mature hematopoietic cells. Inflammation has emerged as a major regulator of both non-malignant and premalignant hematopoiesis. However, our understanding of the mechanisms behind cytokine regulation of BM output are just beginning to develop. In CHAPTER 1 we provide an overview of how BM niches regulate hematopoiesis during steady state and how inflammation perturbs hematopoiesis. We then focus on Interleukin-1 (IL-1) as a paradigm of BM inflammation with pleiotropic effects on hematopoiesis in CHAPTER 2. In CHAPTER 3 we discuss our findings of how IL-1 regulates BM output of granulocytes via a subset of IL-1 receptor (IL-1R1+) expressing vessels. Lastly, we describe our model of this vascular, inflammation-sensing antenna and how it fits into the field of hematopoiesis in CHAPTER 4.
Daniel Lucas, Ph.D. (Committee Chair)
Damien Reynaud, Ph.D. (Committee Member)
Leah Claire Kottyan, Ph.D. (Committee Member)
David Hildeman, Ph.D. (Committee Member)
107 p.
Immunology
bone marrow; hematopoiesis; granulopoiesis; endothelium; vessels; IL-1

Recommended Citations

Citations

  • Slaughter, A. (2023). A Vascular Antenna Senses Inflammation and Orchestrates Emergency Granulopoiesis in the Bone Marrow [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1703168877684916

    APA Style (7th edition)

  • Slaughter, Anastasiya. A Vascular Antenna Senses Inflammation and Orchestrates Emergency Granulopoiesis in the Bone Marrow. 2023. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1703168877684916.

    MLA Style (8th edition)

  • Slaughter, Anastasiya. "A Vascular Antenna Senses Inflammation and Orchestrates Emergency Granulopoiesis in the Bone Marrow." Doctoral dissertation, University of Cincinnati, 2023. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1703168877684916

    Chicago Manual of Style (17th edition)

ucin1703168877684916
524
© 2023, some rights reserved.Creative Commons License A Vascular Antenna Senses Inflammation and Orchestrates Emergency Granulopoiesis in the Bone Marrow by Anastasiya Slaughter is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.
Release 3.2.12