Suppression of human T cell activation by derivatives of glycerol monolaurate

Abstract Glycerol monolaurate (GML), a naturally occurring monoglyceride, is widely used commercially for its antimicrobial properties. Interestingly, several studies have shown that GML not only has antimicrobial properties but is also an anti-inflammatory agent. GML inhibits peripheral blood monon...

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Autores principales:	Micaela G. Fosdick, Pratik Rajesh Chheda, Phuong M. Tran, Alex Wolff, Ronal Peralta, Michael Y. Zhang, Robert Kerns, Jon C. D. Houtman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3f0a0641182b469a9ee320d86e8250d8
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spelling	oai:doaj.org-article:3f0a0641182b469a9ee320d86e8250d82021-12-02T16:55:33ZSuppression of human T cell activation by derivatives of glycerol monolaurate10.1038/s41598-021-88584-y2045-2322https://doaj.org/article/3f0a0641182b469a9ee320d86e8250d82021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88584-yhttps://doaj.org/toc/2045-2322Abstract Glycerol monolaurate (GML), a naturally occurring monoglyceride, is widely used commercially for its antimicrobial properties. Interestingly, several studies have shown that GML not only has antimicrobial properties but is also an anti-inflammatory agent. GML inhibits peripheral blood mononuclear cell proliferation and inhibits T cell receptor (TCR)-induced signaling events. In this study, we perform an extensive structure activity relationship analysis to investigate the structural components of GML necessary for its suppression of human T cell activation. Human T cells were treated with analogs of GML, differing in acyl chain length, head group, linkage of acyl chain, and number of laurate groups. Treated cells were then tested for changes in membrane dynamics, LAT clustering, calcium signaling, and cytokine production. We found that an acyl chain with 12–14 carbons, a polar head group, an ester linkage, and a single laurate group at any position are all necessary for GML to inhibit protein clustering, calcium signaling, and cytokine production. Removing the glycerol head group or replacing the ester linkage with a nitrogen prevented derivative-mediated inhibition of protein cluster formation and calcium signaling, while still inhibiting TCR-induced cytokine production. These findings expand our current understanding of the mechanisms of action of GML and the of GML needed to function as a novel immunosuppressant.Micaela G. FosdickPratik Rajesh ChhedaPhuong M. TranAlex WolffRonal PeraltaMichael Y. ZhangRobert KernsJon C. D. HoutmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Micaela G. Fosdick Pratik Rajesh Chheda Phuong M. Tran Alex Wolff Ronal Peralta Michael Y. Zhang Robert Kerns Jon C. D. Houtman Suppression of human T cell activation by derivatives of glycerol monolaurate
description	Abstract Glycerol monolaurate (GML), a naturally occurring monoglyceride, is widely used commercially for its antimicrobial properties. Interestingly, several studies have shown that GML not only has antimicrobial properties but is also an anti-inflammatory agent. GML inhibits peripheral blood mononuclear cell proliferation and inhibits T cell receptor (TCR)-induced signaling events. In this study, we perform an extensive structure activity relationship analysis to investigate the structural components of GML necessary for its suppression of human T cell activation. Human T cells were treated with analogs of GML, differing in acyl chain length, head group, linkage of acyl chain, and number of laurate groups. Treated cells were then tested for changes in membrane dynamics, LAT clustering, calcium signaling, and cytokine production. We found that an acyl chain with 12–14 carbons, a polar head group, an ester linkage, and a single laurate group at any position are all necessary for GML to inhibit protein clustering, calcium signaling, and cytokine production. Removing the glycerol head group or replacing the ester linkage with a nitrogen prevented derivative-mediated inhibition of protein cluster formation and calcium signaling, while still inhibiting TCR-induced cytokine production. These findings expand our current understanding of the mechanisms of action of GML and the of GML needed to function as a novel immunosuppressant.
format	article
author	Micaela G. Fosdick Pratik Rajesh Chheda Phuong M. Tran Alex Wolff Ronal Peralta Michael Y. Zhang Robert Kerns Jon C. D. Houtman
author_facet	Micaela G. Fosdick Pratik Rajesh Chheda Phuong M. Tran Alex Wolff Ronal Peralta Michael Y. Zhang Robert Kerns Jon C. D. Houtman
author_sort	Micaela G. Fosdick
title	Suppression of human T cell activation by derivatives of glycerol monolaurate
title_short	Suppression of human T cell activation by derivatives of glycerol monolaurate
title_full	Suppression of human T cell activation by derivatives of glycerol monolaurate
title_fullStr	Suppression of human T cell activation by derivatives of glycerol monolaurate
title_full_unstemmed	Suppression of human T cell activation by derivatives of glycerol monolaurate
title_sort	suppression of human t cell activation by derivatives of glycerol monolaurate
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3f0a0641182b469a9ee320d86e8250d8
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Suppression of human T cell activation by derivatives of glycerol monolaurate

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