The cation channel TRPM8 influences the differentiation and function of human monocytes
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2022-09-01
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Journal of Leukocyte Biology
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OXFORD UNIV PRESS
Melbourne Authors
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Medical Biology (W.E.H.I.)
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Journal Article
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Hornsby, E., King, H. W., Peiris, M., Buccafusca, R., Lee, W. Y. J., Wing, E. S., Blackshaw, L. A., Lindsay, J. O. & Stagg, A. J. (2022). The cation channel TRPM8 influences the differentiation and function of human monocytes. Journal of Leukocyte Biology, 112 (3), pp.365-381. https://doi.org/10.1002/JLB.1HI0421-181R.
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Abstract
Monocytes are mononuclear phagocytes that can differentiate to a variety of cell fates under the influence of their microenvironment and hardwired commitment. We found that inhibition of TRPM8 in human blood CD14+ monocytes during a critical 3-h window at the beginning of their differentiation into macrophages led to enhanced survival and LPS-driven TNFα production after 24 h. TRPM8 antagonism also promoted LPS-driven TNFα production in CD14+ monocytes derived from the intestinal mucosa. Macrophages that had been derived for 6 days under blockade of TRPM8 had impaired phagocytic capacity and were transcriptionally distinct. Most of the affected genes were altered in a way that opposed normal monocyte to macrophage differentiation indicating that TRPM8 activity promotes aspects of this differentiation programme. Thus, we reveal a novel role for TRPM8 in regulating human CD14+ monocyte fate and function.