Obermajer, Natasa and Kalinski, Pawel (2012) Generation of myeloid-derived suppressor cells using prostaglandin E2. Transplantation Research 1, p. 15.
|License: Creative Commons Attribution|
PDF - Published Version
Myeloid-derived suppressor cells (MDSCs) are natural immunosuppressive cells and endogenous inhibitors of the immune system. We describe a simple and clinically-compatible method of generating large numbers of MDSCs, using the cultures of peripheral blood-isolated monocytes supplemented with prostaglandin E2 (PGE2). We observed that PGE2 induces endogenous COX2 expression in cultured monocytes, blocking their differentiation into CD1a+ DCs and inducing the expression of IDO1, IL-4Ralpha, NOS2 and IL-10, typical MDSC-associated suppressive factors. The establishment of a positive feedback loop between PGE2 and COX2, the key regulator of PGE2 synthesis is necessary and sufficient to promote the development of CD1a+ DCs to CD14+CD33+CD34+ monocytic MDSCs in GM-CSF/IL-4-supplemented monocyte cultures, for their stability, production of multiple immunosuppressive mediators and CTL-suppressive function. In addition to PGE2, also selective EP2- and EP4-agonists, but not EP3/1 agonists, induce the MDSCs development, suggesting that other activators of the EP2- and EP2-driven signaling pathway (adenylate cyclase/cAMP/PKA/CREB) may be used to promote the development of suppressive cells. Our observations provide for a simple method to generate large numbers of MDSCs for the immunotherapy of autoimmune diseases, chronic inflammatory disorders and transplant rejection.
|Date:||28 September 2012|
|Institutions:||Medicine > Lehrstuhl für Chirurgie|
|Projects:||Open Access Publizieren (DFG)|
|Keywords:||Cancer; COX2; Dendritic cells; Human; Immune dysfunction; Immunotherapy; Myeloid-derived suppressor cells; PGE2; Transplantation|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||23 Oct 2012 06:38|
|Last Modified:||19 Mar 2013 10:09|