Introduction

Myeloid lineage cells have crucial functions in immune responses as well as in the development, homeostasis and remodelling of all tissues; they recognize soluble mediators in the tissue microenvironment and surface ligands expressed on neighbouring cells through multiple receptors. Pattern recognition receptors, such as Toll-like receptors (TLRs), NOD-like receptors and scavenger receptors, signal the presence of molecular patterns that portend microbial invasion or tissue damage. Other receptors perceive the state of the organism and help to set thresholds for cellular responses to each molecular pattern encountered, ultimately controlling the amplitude and duration of the response. By integrating the responses of all receptors, myeloid cells can generate a carefully graded response to a specific set of conditions.

Triggering receptors expressed on myeloid cells (TREMs) are a family of cell-surface receptors expressed broadly on myeloid cells. The first TREM identified, TREM1, was characterized as an amplifier of the immune response that potentiates granulocyte and monocyte responses to microbial products. The TREM family has since been extended to include proteins expressed on granulocytes, monocytes and tissue macrophages, as well as on macrophage and dendritic cell (DC) lines. Generally, TREMs appear to function primarily as modulators that define the threshold and duration of myeloid cell responses. TREMs have been found to have both positive and negative functions in regulating the activation and differentiation of myeloid cells and have been implicated in multiple conditions and diseases.

In this Review, I detail the genomic organization, structure and signalling mechanisms of TREMs, and extensively discuss the functions of TREM1 and TREM2, which are the best-characterized TREMs. I briefly review our knowledge of other, less-investigated TREM family members. Finally, I summarize the challenges that remain in understanding TREM biology and harnessing our knowledge for therapeutic intervention in human diseases.

Please visit the link to learn more about the conference: The biology of TREM receptors