Human Mast Cell Proteome Reveals Unique Lineage, Putative Functions, and Structural Basis for Cell Ablation

Mast cells are rare tissue-resident cells of importance to human allergies. To understand the structural basis of principle mast cell functions, we analyzed the proteome of primary human and mouse mast cells by quantitative mass spectrometry. We identified a mast-cell-specific proteome signature, indicative of a unique lineage, only distantly related to other immune cell types, including innate immune cells. Proteome comparison between human and mouse suggested evolutionary conservation of core mast cell functions. In addition to specific proteases and proteins associated with degranulation and proteoglycan biosynthesis, mast cells expressed proteins potentially involved in interactions with neurons and neurotransmitter metabolism, including cell adhesion molecules, ion channels, and G protein coupled receptors. Toward targeted cell ablation in severe allergic diseases, we used MRGPRX2 for mast cell depletion in human skin biopsies. These proteome analyses suggest a unique role of mast cells in the immune system, probably intertwined with the nervous system. [Display omitted] •Mast cell proteome is unique among immune lineages and conserved from mice to men•Mast cells express proteins potentially involved in neuroimmune interactions•Mast cells lack expression of key innate immune sensors•MRGRPX2 is a mast cell surface protein suitable for ablation of skin mast cells Mast cell functions beyond allergic diseases remain enigmatic. To provide structural information, Plum et al. performed comprehensive proteome analyses on primary human and mouse mast cells, revealing the cells' unique lineage within the immune system, putative roles in neuroimmune interactions, and targets for antibody-mediated mast cell ablation.