A genetically encoded sensor for visualizing leukotriene B4 gradients in vivo

Szimonetta Xénia Tamás, Benoit Thomas Roux, Boldizsár Vámosi, Fabian Gregor Dehne, Anna Török, László Fazekas and Balázs Enyedi ()
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Szimonetta Xénia Tamás: Faculty of Medicine
Benoit Thomas Roux: Faculty of Medicine
Boldizsár Vámosi: Faculty of Medicine
Fabian Gregor Dehne: Faculty of Medicine
Anna Török: Faculty of Medicine
László Fazekas: Faculty of Medicine
Balázs Enyedi: Faculty of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Leukotriene B4 (LTB4) is a potent lipid chemoattractant driving inflammatory responses during host defense, allergy, autoimmune and metabolic diseases. Gradients of LTB4 orchestrate leukocyte recruitment and swarming to sites of tissue damage and infection. How LTB4 gradients form and spread in live tissues to regulate these processes remains largely elusive due to the lack of suitable tools for monitoring LTB4 levels in vivo. Here, we develop GEM-LTB4, a genetically encoded green fluorescent LTB4 biosensor based on the human G-protein-coupled receptor BLT1. GEM-LTB4 shows high sensitivity, specificity and a robust fluorescence increase in response to LTB4 without affecting downstream signaling pathways. We use GEM-LTB4 to measure ex vivo LTB4 production of murine neutrophils. Transgenic expression of GEM-LTB4 in zebrafish allows the real-time visualization of both exogenously applied and endogenously produced LTB4 gradients. GEM-LTB4 thus serves as a broadly applicable tool for analyzing LTB4 dynamics in various experimental systems and model organisms.

Date: 2023
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DOI: 10.1038/s41467-023-40326-6

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