Regulation of human mast cell development

Sammanfattning: Mast cells are multifunctional effector cells of the immune system and are best known for theirparticipation in allergic reactions. The aim of this thesis was to investigate how the stem cell factor(SCF)-dependent development of mast cells from cord blood can be regulated by different factors, and tostudy how immature mast cells circulating in the blood can be recruited into the tissue.In this thesis it was found that flt3 ligand (FL), that has been reported to have many similarities withSCF, does not induce the development of mast cells from cord blood. However, FL support the survivalof hematopoietic progenitor cells and/or cells of the mast cell lineage. In contrast, the hematopoieticgrowth factors IL-3 and GM-CSF inhibit human mast cell development. However, there are progenitorsresistant to the lineage differentiation signals of these cytokines, keeping their potential to differentiate intomature mast cells. Furthermore, retinoic acid (RA) was found to inhibit the development of mast cells,mainly affecting uncommitted progenitors and/or mast cell progenitors. The major finding was that mastcells are less susceptible to inhibitory signals the more mature they are. This thesis also reports functional expression of the chemokine receptor CXCR4 on cells of the mast cell lineage. Its ligand, SDF-1, acts as amast cell chemotaxin and induces migration of progenitors with the capacity to differentiate into mastcells.In conclusion, this thesis shows that certain factors, can influence the development of mast cells aswell as their recruitment into tissues. These findings may be of importance for controlling the number ofmast cells in the tissues, e.g., in allergy, and thereby the severity of the inflammation.