Engraftment, Fate, and Function of HoxB8-Conditional Neutrophil Progenitors in the Unconditioned Murine Host

• Published in: Frontiers in cell and developmental biology 2022-01, Vol.10, p.840894-840894
• Main Authors: Cohen, Joshua T, Danise, Michael, Hinman, Kristina D, Neumann, Brittany M, Johnson, Renita, Wilson, Zachary S, Chorzalska, Anna, Dubielecka, Patrycja M, Lefort, Craig T
• Format: Article
• Language: English
• Subjects: Cell and Developmental Biology; cell therapeutics; engraftment; granulopoeisis; hematopoietic stem and progenitor cell (HSPC); leukocyte recruitment; neutrophils
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2022.840894

The development and use of murine myeloid progenitor cell lines that are conditionally immortalized through expression of HoxB8 has provided a valuable tool for studies of neutrophil biology. Recent work has extended the utility of HoxB8-conditional progenitors to the setting via their transplantation into irradiated mice. Here, we describe the isolation of HoxB8-conditional progenitor cell lines that are unique in their ability to engraft in the naïve host in the absence of conditioning of the hematopoietic niche. Our results indicate that HoxB8-conditional progenitors engraft in a β1 integrin-dependent manner and transiently generate donor-derived mature neutrophils. Furthermore, we show that neutrophils derived from transplanted HoxB8-conditional progenitors are mobilized to the periphery and recruited to sites of inflammation in a manner that depends on the C-X-C chemokine receptor 2 and β2 integrins, the same mechanisms that have been described for recruitment of endogenous primary neutrophils. Together, our studies advance the understanding of HoxB8-conditional neutrophil progenitors and describe an innovative tool that, by virtue of its ability to engraft in the naïve host, will facilitate mechanistic experimentation on neutrophils.