Lin- CD34hi CD117Int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors

Abstract

Mast cells are rare tissue-resident immune cells that are involvedinallergic reactions, and their numbers are increasedinthe lungsofasthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in thetissue.In humans, mast cells can be cultured from multipotent CD34+ progenitor cells. However, a population of distinct precursorcellsthatgiverisetomastcellshas remained undiscovered.Toourknowledge, this is the first report of human lineage-negative (Lin-) CD34hi CD117Int/hi FcεRI+ progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7and developedamast cell-like phenotype, althoughwithaslowcelldivisioncapacityinvitro. IsolatedLin-CD34hi CD117int/hi FcεRI+ blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophilsin whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin-CD34hi CD117int/hi FcεRI+ blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin-CD34hi CD117int/hi FcεRI+ blood mast cell progenitors than asthmatics with normal lung function.