Soluble TLT-1 is a naturally occurring TREM-1 inhibitor and protects mice from hyperresponsiveness and death during sepsis

Triggering receptor expressed on myeloid cells-1 (TREM-1) and TREM-like transcript 1 (TLT-1) belong to the TREM family. TREM-1 is expressed on neutrophils and monocytes/macrophages, and plays a crucial role during the onset of sepsis by cooperating with pattern recognition receptors in a synergistic way, thus amplifying the host immune response. TLT-1 is selectively expressed on activated platelets and is known to facilitate platelet aggregation through binding to fibrinogen. Interestingly, TLT-1 null mice displayed higher plasma cytokines concentrations and death rates than WT mice during experimental sepsis. We identified a 17 amino acid peptide derived from the extracellular part of TLT-1, named LR17, which is responsible for TLT-1 anti-inflammatory properties.