Extracellular ST6GAL1 regulates monocyte-macrophage development and survival.

Michael E Rusiniak, Patrick R Punch, Nitai C Hait, Aparna Maiti, Robert T Burns, Digantkumar Chapla, Kelley W Moremen, Peng Zhao, Lance Wells, Karin Hoffmeister, Joseph T Y Lau

Glycobiology 2022 Jul 13

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Interaction of immune cells with the systemic environment is necessary for the coordinated development and execution of immune responses. Monocyte-macrophage lineage cells reside at the junction of innate and adaptive immunity. Previously we reported that the sialyltransferase ST6GAL1 in the extracellular milieu modulates B cell development and IgG production, granulocyte production, and attenuates acute airway inflammation to bacterial challenge in mouse models. Here, we report that extracellular ST6GAL1 also elicits profound responses in monocyte-macrophage lineage cells. We show that recombinant ST6GAL1 adheres to subsets of thioglycolate-elicited inflammatory cells in the mouse peritoneum and to cultured human monocyte THP-1 cells. Exposure of the inflammatory cells to recombinant ST6GAL1 elicited wholesale changes in the gene expression profile of primary mouse myeloid cells; most notable was the striking up-regulation of monocyte-macrophage and monocyte-derived dendritic cell development pathway signature genes and transcription factors PU.1, NFκB and their target genes, driving increased monocyte-macrophage population and survival ex vivo. In the cultured human monocyte cells, the essential cell surface receptor of the monocyte-macrophage lineage, the M-CSF receptor (M-CSF-R, Csfr1) was a target of extracellular ST6GAL1 catalytic activity. Extracellular ST6GAL1 activated the M-CSF-R and initiated intracellular signaling events, namely, the nuclear translocation of NFκB subunit p65, and phosphorylation of ERK 1/2 and AKT. The findings implicate extracellular ST6GAL1 in monocyte development by a mechanism initiated at the cell surface and support an emerging paradigm of an extracellular glycan-modifying enzyme as a central regulator coordinating immune hematopoietic cell development and function. © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Michael E Rusiniak, Patrick R Punch, Nitai C Hait, Aparna Maiti, Robert T Burns, Digantkumar Chapla, Kelley W Moremen, Peng Zhao, Lance Wells, Karin Hoffmeister, Joseph T Y Lau. Extracellular ST6GAL1 regulates monocyte-macrophage development and survival. Glycobiology. 2022 Jul 13;32(8):701-711