Abstract
Cell-cell communication is critical for the development and function of multicellular organisms. A crucial means by which cells communicate with one another is physical interactions between receptors on one cell and their ligands on a neighboring cell. Trans ligand:receptor interactions activate the receptor, ultimately leading to changes in the fate of the receptor-expressing cells. Such trans signaling is known to be critical for the functions of cells in the nervous and immune systems, among others. Historically, trans interactions are the primary conceptual framework for understanding cell-cell communication. However, cells often coexpress many receptors and ligands, and a subset of these has been reported to interact in cis and profoundly impact cell functions. Cis interactions likely constitute a fundamental, understudied regulatory mechanism in cell biology. Here, I discuss how cis interactions between membrane receptors and ligands regulate immune cell functions, and I also highlight outstanding questions in the field.