Molecular regulation of structural organization of lymphatic organs

The cytokines play a significant role in biogenesis and structural organization of lymphatic organs (LO). Mutant mice deficient in some cytokines show the absence of LO or their profound disorganization. However, molecular mechanisms which regulate the development of certain types of nonlymphoid cells and their integration into the structure of LO during embryonic/postnatal and adult period are not known. Thus, our aim is to investigate the role of cytokines in development of different nonlymphoid cells and structural organization of primary and secondary LO at several planes: a) development of thymic metallophilic macrophages and their positioning in the cortico-medullary zone during embryonic and postnatal period, b) development and positioning of these cells in the thymus of mice deficient in different cytokines or their receptors, c) development and functional morphology of medullary thymic epithelial cells in CCR7-deficient mice, d) development, maturation and positioning of follicular dendritic cells and marginal metallophilic macrophages in the splenic white pulp after application of lipopolysaccharide, e) role of lymphotoxin-beta and tumor necrosis factor-alpha in structural organization of LO during adult period using splenic transplantation as an experimental model. Histochemical, enzymehistochemical, immunocytochemical and morphometric methods, electron microscopy, flow cytometry and tissue microdissection in combination with polymerase chain reaction will be used.