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TLT-1 regulates leukocyte activation and controls inflammatory response during polymicrobial sepsis

Abstract : The Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) plays a crucial role during the onset of sepsis by amplifying the host immune response. The TREM-Like Transcript-1 (TLT-1) belongs to the TREM family, is selectively expressed on activated platelets, and is known to facilitate platelet aggregation through binding to fibrinogen. Here we show that a soluble form of TLT-1 is implicated in the regulation of inflammation during sepsis by dampening leukocytes activation and modulating platelet-neutrophil crosstalk. A 17-aa sequence of the TLT-1 extracellular domain (LR17) is responsible for this activity through competition with the TREM-1 ligand. While early or late LR17 treatment of septic mice improves survival, treml-1-/- animals are highly susceptible to polymicrobial infection. The present findings identify platelet derived sTLT-1 as a potent endogenous regulator of sepsis associated inflammation and open new therapeutic perspectives
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https://hal.univ-lorraine.fr/tel-01746319
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 10:31:03 AM
Last modification on : Friday, May 21, 2021 - 2:57:07 PM

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  • HAL Id : tel-01746319, version 1

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Marc Derive. TLT-1 regulates leukocyte activation and controls inflammatory response during polymicrobial sepsis. Human health and pathology. Université Henri Poincaré - Nancy 1, 2011. English. ⟨NNT : 2011NAN10151⟩. ⟨tel-01746319⟩

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