Adenosine and its Impact on Neonatal Immune Effector Cells

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Dokumentart: PhDThesis
Date: 2022-11-27
Language: English
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Biochemie
Advisor: Gille, Christian (PD Dr.)
Day of Oral Examination: 2020-11-27
DDC Classifikation: 500 - Natural sciences and mathematics
Keywords: Neugeborenensepsis
Other Keywords:
neonatal immune system
Myeloid-derived suppressor cells
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Neonatal sepsis is a leading cause of neonatal morbidity and mortality. This is partially due to immaturity of the neonatal immune system as a remnant of prenatal development when the activity of neonatal immune system has to be downregulated and feto-maternal tolerance has to be maintained. Postnatally, the switch from immunosuppression to immunocompetence may be delayed because of persisting cellular mechanisms acting inhibitory such as presence of myeloid-derived suppressor cells (MDSC), as well as soluble factors. In adults extracellular adenosine has been shown to act immunosuppressive. In this project, the role of adenosine for neonatal immunosuppression was analyzed. The role of adenosine in neonates is only incompletely understood. My results show that adenosine is produced by neonatal immune effector cells and that it can inhibit neonatal immune reactions either directly through T cell proliferation inhibition or indirectly via MDSC induction and their activation by induction of indoleamine-2,3-dioxygenase (IDO) production. Pleiotropism of adenosine may therefore be one of the key players in the maintaining of feto-maternal tolerance and neonatal immunosuppression. According to the results of my investigations, adenosine may be a promising target for immunotherapy in the neonate.

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