La multimérisation de TREM-1 est essentielle pour son activation sur les monocytes et les neutrophiles

Abstract : Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a receptor expressed on innate immune cells which amplifies inflammatory signals initially triggered by TLRs (Toll-like receptors) and TREM-1 has been characterized as a major player in the pathophysiology of acute and chronic inflammatory diseases. Currently, the molecular mechanisms leading to the activation of TREM-1 remain unknown. We have developed specific tools to stimulate TREM-1 in a monovalent and divalent way. Here we show that TREM-1 is activated by multimerization and is differentially regulated on neutrophils and monocytes. Indeed, TREM-1 activation on primary human monocytes by LPS required a two-step process while one is required on neutrophils. Using proteomic approaches, we have confirmed that TREM-1 ectodomain dimerizes in solution. Furthermore, the multimerization seems to be mediated by the natural ligand of TREM-1, which is released by LPS activated neutrophils. Collectively, our findings uncover molecular mechanisms leading to TREM-1 and its ligand interaction, painting the way of new therapeutics
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https://hal.univ-lorraine.fr/tel-01925170
Contributor : Thèses Ul <>
Submitted on : Friday, November 16, 2018 - 2:58:16 PM
Last modification on : Saturday, November 17, 2018 - 1:17:10 AM

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  • HAL Id : tel-01925170, version 1

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Kevin Carrasco. La multimérisation de TREM-1 est essentielle pour son activation sur les monocytes et les neutrophiles. Biochimie, Biologie Moléculaire. Université de Lorraine, 2018. Français. ⟨NNT : 2018LORR0004⟩. ⟨tel-01925170⟩

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