Early development and functional properties of tryptase/chymase double-positive mast cells from human pluripotent stem cells

Mast cells (MCs) play a pivotal role in the hypersensitivity reaction by regulating the innate and adaptive immune responses. Humans have two types of MCs. The first type, termed MCTC, is found in the skin and other connective tissues and expresses both tryptase and chymase, while the second, termed MCT, which only expresses tryptase, is found primarily in the mucosa. MCs induced from human adult-type CD34(+) cells are reported to be of the MCT type, but the development of MCs during embryonic/fetal stages is largely unknown. Using an efficient coculture system, we identified that a CD34(+)c-kit(+) cell population, which appeared prior to the emergence of CD34(+)CD45(+) hematopoietic stem and progenitor cells (HSPCs), stimulated robust production of pure Tryptase(+)Chymase(+) MCs (MC(TC)s). Single-cell analysis revealed dual development directions of CD34(+)c-kit(+) progenitors, with one lineage developing into erythro-myeloid progenitors (EMP) and the other lineage developing into HSPC. Interestingly, MC(TC)s derived from early CD34(+)c-kit(+) cells exhibited strong histamine release and immune response functions. Particularly, robust release of IL-17 suggested that these early developing tissue-type MC(TC)s could play a central role in tumor immunity. These findings could help elucidate the mechanisms controlling early development of MC(TC)s and have significant therapeutic implications.

Automated summary

Research has shown that there are two types of mast cells in humans, one expressing tryptase and chymase found in the skin and connective tissues, and another type primarily expressing tryptase found in the mucosa. Through an efficient coculture system, a cell population of CD34(+)c-kit(+) cells was found to stimulate the production of MC(TC)s, which exhibit strong histamine release and immune response functions. This early developing tissue-type MC(TC)s may play a significant role in tumor immunity, with the release of IL-17 suggesting a central role in this immune response.