The cation channel TRPM8 influences the differentiation and function of human monocytes

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Eve Hornsby¹  Hamish W. King¹  Madusha Peiris²  Roberto Buccafusca³  Wing-Yiu Jason Lee¹  Elinor S. Wing¹  L. Ashley Blackshaw²  James O. Lindsay¹  Andrew J. Stagg¹ 

[1] Centre for Immunobiology & Barts and The London School of Medicine & Dentistry, Queen Mary University of London;Centre for Neuroscience & Trauma, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London;School of Biological and Chemical Sciences, Queen Mary University of London;Department of Gastroenterology, Barts Health NHS Trust, The Royal London Hospital

关键词: LPS;    monocyte-derived macrophage;    phagocytosis;    TRP channels;   

DOI  :  10.1002/JLB.1HI0421-181R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

CC BY